The review also looks forward to the arrival of newly designed molecules that mimic the action of insulin while avoiding triggering an allergic response. In addition new modes of drug delivery, such as continuous subcutaneous insulin infusion (CSII), may help, and early reports suggest that CSII can help people who have previously had an allergic reaction to insulin.

In the 1950s and 1960s more than half of patients who used insulin experienced some form of allergic reaction. This has reduced considerably, but reports show that 0.1% to 3.0% of people still produce reactions that range from mild irritation to life-threatening incidents. Originally insulin was harvested from animals, and advanced purification now makes this safer to use. The gene for human insulin has been sequenced, and the sequence placed in bacteria. These modified organisms then produce the human insulin protein which can then be purified and used for therapy. Fewer people react to this recombinant insulin' because this is the human protein. Now that scientists know the gene sequence, the shape of the insulin molecule, and the shape of the active site of the molecule, they can start to redesign it. The idea is to create a molecule that retains the action of insulin, but does not excite the human immune response system. This way it will be active, but will not cause an allergic reaction. One potential reason for adverse reaction is that insulin is often injected in sudden doses. This gives unnaturally high peaks and troughs of the hormone. To avoid this variation, pumps have been developed that slowly infuse the hormone throughout the day. Early results on these pumps are promising.

"Our review shows just how much progress has been made in reducing allergic reactions to insulin, but more excitingly it shows that there are definite hopes of improving the situation even further," says lead author Regis Radermecker, who works at the Division of Diabetes, Nutrition and Metabolic Disorders at the University of Li ge, Belgium.

interscience.wiley/journal/dmrr

Currently, physicians manage cultured skin graft infections during the early healing period by continually wrapping the wound in dressings soaked in antimicrobial drugs. Although this protects the grafts, Supp says, it can also contribute to the emergence of drug-resistant strains of bacteria.

"When you give the patient the same drug topically and orally, the risk for drug-resistant bacteria to emerge is greatly increased," says Supp. "We need alternative methods for combating infection in burn patients.

In this three-year laboratory study, Supp isolated the HBD4 gene from donated tissue samples and transferred it into surface skin cells (keratinocytes) to give them enhanced infection-fighting abilities. These cells were then infected with pseudomonas aeruginosa, a type of bacteria found commonly in hospitals, and allowed to incubate. Analysis revealed that the genetically altered cells containing HBD4 were more resistant to microbial infections than the unaltered cells.

"If it proves effective in additional testing," Supp predicts, "this type of gene therapy could be a promising alternative infection control method for burn wounds."

Researchers hope to begin testing this approach in an animal model in early 2007.

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