Beaker bytes
Celebrex may prevent
surgical adhesions
COX-2 inhibitors, known best as arthritis drugs, recently came under scrutiny with evidence that chronic use may lead to heart attack and stroke. But a discovery at Children's Hospital Boston suggests that short-term use of one COX-2 inhibitor, Celebrex, is potentially of great value to surgeons.
Surgery's Mark Puder, MD, PhD, and Arin Greene, MD, found evidence that the drug prevents adhesions—bands of scar tissue that bind two internal body surfaces—in mice after surgery. They're part of normal healing, but when tissues fuse that shouldn't, serious pain and complications, such as bowel obstruction and infertility, can result. Adhesions form in 55 to 90 percent of surgical patients, depending on the procedure, and there's currently no good preventive treatment.
In the Children's study, soon to appear in the Annals of Surgery, mice receiving Celebrex for 10 days after abdominal surgery were much less likely to have adhesions than those given either a placebo or a non-selective COX-2 inhibitor, like ibuprofen or aspirin. Six of 11 Celebrex-treated mice were completely adhesion-free. Based on these findings, Puder is now planning a multi-institutional clinical trial of Celebrex in adult surgical patients.
A strategic shape change on a deadly virus
Human immunodeficiency virus (HIV)—the virus that causes AIDS—is notorious for evading attack, as is evident in that there's still no vaccine or fully effective drug treatment. But now, structural biologists Stephen Harrison, PhD, and Bing Chen, PhD, in Children's Hospital Boston's Laboratory of Molecular Medicine, have shown how a key part of HIV changes shape’Äîa change that not only helps it hide from the immune system, but is also key to enabling the virus to infect cells.
Harrison and Chen focused on gp120, a protein on HIV's surface that binds to a cell's CD4 receptor. Once bound, gp120 rearranges itself, signaling a companion HIV protein, gp41, to launch a series of maneuvers that allow HIV to fuse its outer membrane with that of the target cell. This fusion lets HIV enter the cell and begin replicating.
While the structure of gp120 after the shape change was determined several years ago by another group, Harrison and Chen have now extended the picture. They've obtained high-resolution, three-dimensional images of gp120 before the change by X-raying a crystallized form of the protein. (The images can be seen in the February 24 issue of the journal Nature or online at www.childrenshospital.org/research.)
"Knowing how gp120 changes shape might be helpful in inhibiting HIV’Äîby using compounds that stop the shape change," says Harrison, adding that some HIV inhibitors already in development seem to have this ability. "We can also compare the bound and unbound forms and try to understand whether there are any immunologic properties that differ, which might provide a route to new vaccine strategies."
