Purpose: To describe the MR appearance of the normal appendix and the MR imaging characteristics of acute appendicitis with correlation to pathological severity. Materials and Methods:A total of 20 volunteers participated in this study to demonstrate normal appendices by MR imaging. A total of 37 consecutive patients with clinically diagnosed acute appendicitis were also scanned. T1-weighted (T1WI) spin-echo images, T2-weighted (T2WI) fast spin-echo, and fat-suppressed spectral presaturation inversion recovery T2-weighted (T2SPIR) fast spin-echo images were obtained. The MR criteria for considering acute appendicitis were as follows: 1) thickening of the appendiceal wall with high intensity on T2WI or T2SPIR; 2) dilated lumen filled with high intensity material on T2WI or T2SPIR; and 3) increased intensity of periappendiceal tissue on T2WI or T2SPIR. Results:The visibility of a normal appendix on MR imaging was 90% (18/20). It appeared as a cord-like structure of medium intensity without fluid collection in the lumen. A total of 30 cases with clinically diagnosed acute appendicitis had positive MR findings and all except one were pathologically proven. The one had cecal diverticulitis. These cases demonstrated filled lumen, with a hypointense wall on T1WI and slightly hyperintense on T2WI or T2SPIR. MR findings correlated well with pathological severity, especially a thicker wall, periappendiceal high intensity, and ascites were useful for suspecting severe appendicitis. Conclusion:Correct diagnosis of acute appendicitis was obtained with MRI, and correlated well with its pathological severity. MRI is a powerful alternative for diagnosing acute appendicitis especially for the patients in whom the radiation is major concern. ACUTE APPENDICITIS is one of the most common abdominal diseases and presents as an acute abdomen. The diagnosis is usually based on clinical and laboratory findings, however, approximately one-third of patients with acute appendicitis present with atypical clinical symptoms. This confusion leads to a high prevalence of unnecessary laparotomy, reported at 6% to 16% (1-5). The other cases demonstrate atypical and nonspecific symptoms shared with other abdominal diseases including cholecystitis, gastritis, enterocolitis, diverticulitis, mesenteric adenitis, gynecological disease (e.g., pelvic inflammatory disease [PID], tubo-ovarian abscess, ovarian cyst or torsion, endometriosis, degenerating uterine leiomyoma), and urological disorders (6 -12). In such clinically questionable cases, it is not uncommon that radiological evaluations provide useful information in making a differential diagnosis. An appropriate imaging procedure can prevent surgery delays and minimize the rate of negative laparotomies. Currently, the imaging modalities chosen to demonstrate an inflamed appendix, as well as its complications, are ultrasound (US) and computed tomography (CT). However, MR has not been applied to acute appendicitis.The first objective of this study was to describe the MR appearances of the normal appe...

Glucagon-like peptide-1 (GLP-1) is an incretin peptide that plays a crucial role in lowering blood glucose levels and holds promise for treating type II diabetes. In this study, we synthesized GLP-1 derivatives that were conjugated with glycosaminoglycans (GAGs), i.e., chondroitin (CH) or heparosan (HPN), to address the major limitation in their clinical use of GLP-1, which is its short half-life in the body. After exploring a variety of CHs with different molecular sizes and heterobifunctional linkers having different alkyl chains, we obtained CH-conjugated GLP-1 derivatives that stayed in blood circulation much longer (T1/2 elim > 25 h) than unconjugated GLP-1 and showed blood glucose-lowering efficacy up to 120 h after subcutaneous injection in mice. By using the same optimized linker design, we eventually obtained a HPN-conjugated GLP-1 derivative with efficacy lasting 144 h. These results demonstrate that conjugation with GAG is a promising strategy for improving the duration of peptide drugs.

A novel, long-acting insulin conjugate was developed by modification with a glycosaminoglycan (GAG; i.e., chondroitin [CH] or heparosan [HPN]) at different positions (GlyA1, LysB29, or both) via different linkers with varying arm lengths. The in vitro glucose uptake-enhancing activity of conjugates inversely correlated with the circulatory in vivo half-life in mice and was affected primarily by the conjugation position rather than linker arm length. Conjugation at GlyA1, which provided the best balanced profile of in vitro activity and circulation period in mice, also provided the strongest glucose-lowering efficacy, exhibiting 12 h durability, which was superior to that of insulin glargine and comparable to that of insulin degludec in streptozotocin (STZ)-treated mice. The use of different GAGs did not significantly affect blood circulation or efficacy in mice; however, blood levels of CH-conjugated insulin and efficacy were lower in rats, indicating species differences in the performance of CH. Finally, optimal activity was obtained by conjugation with HPN at GlyA1 using a C3 linker. These results demonstrate the applicability of GAG modification for prolonging the efficacy of peptide drugs, similar to our previous application to glucagon-like peptide 1.

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