PubMed · 4102899
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
A L Mills. 1971. Lead in the environment.. https://pubmed.ncbi.nlm.nih.gov/4102899/
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
In view of the known problems that diabetic recipients have with drug absorption and of the potential advantages of the microemulsion formulation of cyclosporine (Neoral), 17 previously diabetic recipients of simultaneous pancreas and kidney allografts were studied before and after conversion from Sandimmune (SIM) to Neoral (NEO) formulations of cyclosporine a mean of 4.75 +/- 2.0 years after transplantation. The aims of this study were to determine whether there were changes in the absorption profiles using the 2 formulations and to analyze the safety of conversion from SIM to NEO on a 1:1 ratio. Pharmacokinetic, clinical, and renal function parameters were measured 2 weeks before, and 2 and 4 weeks after conversion. Pharmacokinetics demonstrated that, when taking SIM, only 5 patients had "good absorption" (maximal concentration >500 ng/ml and time to maximal concentration < / = 2 hr), but after conversion to NEO, 14 at week +2, and 13 at week +4 were good absorbers (P<0.02 and <0.01, respectively). There was a 50% reduction in the time to maximal blood concentration (from 3.2 +/- 1.9 hr with SIM, to 1.8 +/- 1.3 hr on NEO [P<0.007]) and a 36% increase in trough and a 143% increase (P<0.01) in maximal blood concentrations, although the 9-hr cyclosporine AUC showed an 89% increase (P<0.01). There was an 18% mean reduction in dose per kilogram prescribed 4 weeks after conversion. Renal function, measured by serum creatinine and technecium-99m diethylenetriamine pentaacetic acid glomerular filtration rate, was not altered and no adverse events were attributed to NEO. This study confirmed that previously diabetic recipients of simultaneous renal pancreas allografts had variable and poor absorption of cyclosporine using conventional Sandimmune and that this absorption was improved by conversion to Neoral.
Peroxisomal long-chain 2-hydroxy-acid oxidase, an FMN-dependent enzyme, catalyzes the oxidation of a variety of L-2-hydroxy acids into keto acids at the expense of oxygen. We recently reported the cloning and sequencing of its CDNA and the existence of a weakly expressed isozyme [Belmouden, A., Le, K. H. D., Lederer, F. & Garchon, H. J. (1993) Eur. J. Biochem. 214, 17-251. This isozyme, beta 2 differs from the major one in having a three-residue insertion, -VRK-, in loop 4 of the beta 8 alpha 8 barrel. In the crystal structures of homologous flavocytochrome beta 2, and glycolate oxidase, the corresponding region of loop 4 is disordered. We now report on the constitutive high-level expression of isozymes beta 1, and beta 2 in Escherichia coli under control of the lambda pL promoter, and on the influence of the E. coli genetic background and the growth medium on the expression level. We describe the properties of isozyme beta 2 and compare them with those of pure isoform beta 1. The visible spectra of the purified enzymes differ in the position of the near-ultraviolet band of the prosthetic group. pH titration studies indicate that the FMN ionizes at N3 at a lower pH than free flavin and that there is a small pKa difference between the isozymes. To our knowledge, the only other known case of a lowered pKa for the protein-bound flavin is that of glycolate oxidase. In the CD spectra of the FMN region, a marked difference between isozymes in the 270-300-nm region appears to be related to the pKa difference for the N3-H bond. Kinetic parameters for a number of substrates and inhibitors are indistinguishable within the limits of experimental error, with the exception of values for kcat for mandelate (the most active substrate), Km for hydroxyhippurate (a new substrate), Ki for cinnamate and oxalate, and Kd for sulfite. The differences are no larger than twofold. The foregoing comparison between isozymes beta 1 and beta 2 shows that the naturally engineered insertion in loop 4 exerts some influence on the flavin spectral properties and the active-site reactivity. Since the corresponding loop 4 regions in the three-dimensional structures of flavocytochrome 2 and glycolate oxidase are 1.5-2.0 nm removed from the flavin, it would appear either that loop 4 has a very different conformation in hydroxy-acid oxidase, or that it may interact with the active site due to mobility.
Animal-type photolyases have very limited sequence homology to microbial-type photolyases. We wanted to find out whether the two types of enzymes have different or similar biochemical and photochemical properties. In particular, the chromophore/cofactor composition of animal photolyases is of special interest since the presence and nature of a second chromophore in these enzymes are not known in contrast to the microbial photolyases which contain FAD cofactor, and folate or deazaflavin as second chromophores. We overproduced the Drosophila melanogaster photolyase in Escherichia coli using the cloned gene. The enzyme contains FAD and folate and thus belongs in the folate class of enzymes but with an action spectrum peak at 420 nm.