Progress toward re‐engineering non‐ribosomal peptide synthetase proteins: a potential new source of pharmacological agents

Many important pharmaceutical agents, including vancomycin, bleomycin, cyclosporin, and several antibiotics, are produced by non‐ribosomal peptide synthetase (NRPS) enzymes in microorganisms. The NRPS pathway produces an extensive library of products using multienzyme complexes acting in an assembly‐line fashion. Engineering an NRPS system to produce an even greater variety of products, some of which may also have beneficial therapeutic value, would be an enormous advantage. Several approaches have been successful in generating novel NRPS products: mutational biosynthesis during which nonnatural substrates are fed to an organism; domain and module swapping between different species to generate hybrid enzymes; and rational site‐directed mutagenesis, based either on phylogeny or computational prediction, intended to switch substrate specificity and produce altered products. This review will highlight the progress in these areas and describe research in the future that will extend the capacity for re‐engineering NRPS systems. Drug Dev. Res. 66:9–18, 2006. © 2006 Wiley‐Liss, Inc.     

Tc-99m HMPAO SPECT imaging of the central nervous system in tuberous sclerosis

Tc-99m HMPAO was used to evaluate cerebral perfusion in a patient with tuberous sclerosis. The SPECT images demonstrated reduced HMPAO uptake in regions corresponding with MRI-confirmed locations of cortical tubers. These results indicate that the lesions are characterized by vascular perfusion deficits and support the hypothesis that cortical tubers result from developmental abnormalities of the embryonic central nervous system.     

Pediatric tissue and organ transplantation in Florida

Fifty to 100 children receive transplanted kidneys, hearts, livers, or bone marrow in Florida each year and many more bone allografts or other tissues (skin, cornea). Children are in the minority of the total solid organ transplantation but those with successful transplants are strong proponents of the procedure. Many (liver or heart failure) would have died without transplantation; others (kidney failure) would have lived but been tied to dialysis for life. The success rate varies with the organ or tissue transplanted. Some children return to a completely normal life without the need for immunosuppressive medications. Others require them continually. Cyclosporine, azathioprine and prednisone are the most frequently used. Rejection continues to be the leading cause of graft loss. Major impediments to solid organ transplantation are the paucity of acceptable organs and the high cost associated with maintenance of transplant patients.     

Epilation of hair-bearing urethral grafts using the neodymium:YAG surgical laser

Nonhair-bearing skin should be used when grafting is necessary during urethroplasty for stricture or hypospadias repair. Occasionally, this is not possible or hair-bearing skin is used inadvertently. Traditionally, electrocoagulation has been the method used for epilation when intraluminal hair has become a problem, such as interfering with flow, as a focus for recurrent urinary tract infection or acting as a nidus for calculus formation. Electrocautery also is performed during grafting in an attempt to prevent the growth of hair when hair-bearing skin is used. Unfortunately, due to lack of penetration the hair follicles are not destroyed and the epilating procedure fails or is only partially successful. The neodymium:YAG surgical laser can photocoagulate tissue to a depth up to 5.0 mm, and thus, has the ability to destroy hair follicles. We report 4 cases presenting with clinical problems directly related to hair-bearing urethral grafts successfully treated by neodymium:YAG laser epilation.