20 kDa PEGylated Adrenomedullin as a New Therapeutic Candidate for Inflammatory Bowel Disease
Abstract
:1. Introduction
2. Results
2.1. Synthesis and Characterization of 20kPEG-AM
2.2. Cell Culture Experiments
2.3. Plasma Levels of 20kPEG-AM Following Subcutaneous Administration in Mice
2.4. Induction of DSS Colitis and Treatment with 20kPEG-AM
3. Discussion
4. Materials and Methods
4.1. Analysis of 20kPEG-AM
4.2. Cell Culture Experiments
4.3. Animal Experiments
4.3.1. Plasma Concentration of 20kPEG-AM Following Subcutaneous Administration in Mice
4.3.2. Induction of DSS Colitis and Treatment with 20kPEG-AM
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Amino Acid (Expected Residues/Molecule) Residues/Molecule | |||
---|---|---|---|
Asp (6) 6.00 | Thr (3) 2.92 | Ser (4) 3.63 | Glu (6) 5.99 |
Gly (4) 3.96 | Ala (2) 1.99 | Cys (2) 1.85 | Val (2) 2.01 |
Met (1) 0.93 | Ile (2) 1.96 | Leu (2) 2.00 | Tyr (3) 2.84 |
Phe (4) 3.97 | Lys (4) 3.98 | NH3 (10) 10.72 | |
His (1) 1.03 | Arg (4) 4.01 | Pro (2) 2.03 |
Score | Stool Consistency | Bloody Stool | Bodyweight Reduction |
---|---|---|---|
0 | Normal | No blood | No reduction |
1 | 1–5% reduction | ||
2 | Soft | Fecal occult blood | 5–10% reduction |
3 | 10–20% reduction | ||
4 | Diarrhea | Mucus and bloody stool |
Inflammatory Cell Infiltrate | Intestinal Architecture | ||||
---|---|---|---|---|---|
Severity | Extent | Score 1 | Epithelial Changes | Mucosal Architecture | Score 2 |
Mild | Mucosa | 1 | Focal erosions | 1 | |
Moderate | Mucosa and submucosa | 2 | Erosions | ± Focal ulcerations | 2 |
Marked | Transmural | 3 | Extended ulcerations ± granulation tissue ± pseudopolyps | 3 | |
Sum of scores 1 and 2: | 0–6 |
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Miki, G.; Kuroishi, N.; Tokashiki, M.; Nagata, S.; Tamura, M.; Yoshiya, T.; Yoshizawa-Kumagaye, K.; Ashizuka, S.; Kato, J.; Yamasaki, M.; et al. 20 kDa PEGylated Adrenomedullin as a New Therapeutic Candidate for Inflammatory Bowel Disease. Gastrointest. Disord. 2020, 2, 366-377. https://doi.org/10.3390/gidisord2040033
Miki G, Kuroishi N, Tokashiki M, Nagata S, Tamura M, Yoshiya T, Yoshizawa-Kumagaye K, Ashizuka S, Kato J, Yamasaki M, et al. 20 kDa PEGylated Adrenomedullin as a New Therapeutic Candidate for Inflammatory Bowel Disease. Gastrointestinal Disorders. 2020; 2(4):366-377. https://doi.org/10.3390/gidisord2040033
Chicago/Turabian StyleMiki, Goro, Nobuko Kuroishi, Mariko Tokashiki, Sayaka Nagata, Masaji Tamura, Taku Yoshiya, Kumiko Yoshizawa-Kumagaye, Shinya Ashizuka, Joji Kato, Motoo Yamasaki, and et al. 2020. "20 kDa PEGylated Adrenomedullin as a New Therapeutic Candidate for Inflammatory Bowel Disease" Gastrointestinal Disorders 2, no. 4: 366-377. https://doi.org/10.3390/gidisord2040033