1.Molecular Approach to Allergy Diagnosis and Therapy.
Fatima FERREIRA ; Martin WOLF ; Michael WALLNER
Yonsei Medical Journal 2014;55(4):839-852
Presently, allergy diagnosis and therapy procedures are undergoing a transition phase in which allergen extracts are being step-by-step replaced by molecule-based products. The new developments will allow clinicians to obtain detailed information on sensitization patterns, more accurate interpretation of allergic symptoms, and thus improved patients' management. In this respect, recombinant technology has been applied to develop this new generation of molecule-based allergy products. The use of recombinant allergens allows full validation of identity, quantity, homogeneity, structure, aggregation, solubility, stability, IgE-binding and the biologic potency of the products. In contrast, such parameters are extremely difficult to assay and standardize for extract-based products. In addition to the possibility of bulk production of wild type molecules for diagnostic purposes, recombinant technology opened the possibility of developing safer and more efficacious products for allergy therapy. A number of molecule-based hypoallergenic preparations have already been successfully evaluated in clinical trials, bringing forward the next generation of allergy vaccines. In this contribution, we review the latest developments in allergen characterization, molecule-based allergy diagnosis, and the application of recombinant allergens in therapeutic setups. A comprehensive overview of clinical trials using recombinant allergens as well as synthetic peptides is presented.
Allergens/*immunology
;
Humans
;
Hypersensitivity/*immunology/*therapy
;
Immunotherapy/methods
;
Recombinant Proteins/immunology
2.Molecular Approach to Allergy Diagnosis and Therapy.
Fatima FERREIRA ; Martin WOLF ; Michael WALLNER
Yonsei Medical Journal 2014;55(4):839-852
Presently, allergy diagnosis and therapy procedures are undergoing a transition phase in which allergen extracts are being step-by-step replaced by molecule-based products. The new developments will allow clinicians to obtain detailed information on sensitization patterns, more accurate interpretation of allergic symptoms, and thus improved patients' management. In this respect, recombinant technology has been applied to develop this new generation of molecule-based allergy products. The use of recombinant allergens allows full validation of identity, quantity, homogeneity, structure, aggregation, solubility, stability, IgE-binding and the biologic potency of the products. In contrast, such parameters are extremely difficult to assay and standardize for extract-based products. In addition to the possibility of bulk production of wild type molecules for diagnostic purposes, recombinant technology opened the possibility of developing safer and more efficacious products for allergy therapy. A number of molecule-based hypoallergenic preparations have already been successfully evaluated in clinical trials, bringing forward the next generation of allergy vaccines. In this contribution, we review the latest developments in allergen characterization, molecule-based allergy diagnosis, and the application of recombinant allergens in therapeutic setups. A comprehensive overview of clinical trials using recombinant allergens as well as synthetic peptides is presented.
Allergens/*immunology
;
Humans
;
Hypersensitivity/*immunology/*therapy
;
Immunotherapy/methods
;
Recombinant Proteins/immunology
3.Effects of Short Term Adiponectin Receptor Agonism on Cardiac Function and Energetics in Diabetic db/db Mice
Aleksandre TARKHNISHVILI ; Christoph KOENTGES ; Katharina PFEIL ; Johannes GOLLMER ; Nikole J BYRNE ; Ivan VOSKO ; Julia LUEG ; Laura VOGELBACHER ; Stephan BIRKLE ; Sibai TANG ; Timothy Bon-Nawul MWINYELLA ; Michael M HOFFMANN ; Katja E ODENING ; Nathaly Anto MICHEL ; Dennis WOLF ; Peter STACHON ; Ingo HILGENDORF ; Markus WALLNER ; Senka LJUBOJEVIC-HOLZER ; Dirk von LEWINSKI ; Peter RAINER ; Simon SEDEJ ; Harald SOURIJ ; Christoph BODE ; Andreas ZIRLIK ; Heiko BUGGER
Journal of Lipid and Atherosclerosis 2022;11(2):161-177
Objective:
Impaired cardiac efficiency is a hallmark of diabetic cardiomyopathy in models of type 2 diabetes. Adiponectin receptor 1 (AdipoR1) deficiency impairs cardiac efficiency in non-diabetic mice, suggesting that hypoadiponectinemia in type 2 diabetes may contribute to impaired cardiac efficiency due to compromised AdipoR1 signaling. Thus, we investigated whether targeting cardiac adiponectin receptors may improve cardiac function and energetics, and attenuate diabetic cardiomyopathy in type 2 diabetic mice.
Methods:
A non-selective adiponectin receptor agonist, AdipoRon, and vehicle were injected intraperitoneally into Eight-week-old db/db or C57BLKS/J mice for 10 days. Cardiac morphology and function were evaluated by echocardiography and working heart perfusions.
Results:
Based on echocardiography, AdipoRon treatment did not alter ejection fraction, left ventricular diameters or left ventricular wall thickness in db/db mice compared to vehicle-treated mice. In isolated working hearts, an impairment in cardiac output and efficiency in db/db mice was not improved by AdipoRon. Mitochondrial respiratory capacity, respiration in the presence of oligomycin, and 4-hydroxynonenal levels were similar among all groups. However, AdipoRon induced a marked shift in the substrate oxidation pattern in db/db mice towards increased reliance on glucose utilization. In parallel, the diabetes-associated increase in serum triglyceride levels in vehicle-treated db/db mice was blunted by AdipoRon treatment, while an increase in myocardial triglycerides in vehicle-treated db/db mice was not altered by AdipoRon treatment.
Conclusion
AdipoRon treatment shifts myocardial substrate preference towards increased glucose utilization, likely by decreasing fatty acid delivery to the heart, but was not sufficient to improve cardiac output and efficiency in db/db mice.