A reverse-phase high pressure liquid chromatographic method for the detection and quantitation of unchanged ascorbic acid in human urine is described. Twenty-four hour ascorbate excretion profiles from nine subjects were determined. The urinary excretion profiles for orally ingested and intravenously infused ascorbic acid in these nine subjects are compared.

Isopenicillin N synthase (IPNS) is a non-haem iron dependent dioxygenase which catalyses the oxidative conversion of anddelta;-(L-andalpha;-aminoadipoyl)-L-cysteinyl-D-valine (ACV) to isopenicillin N (IPN). Sequence comparisons between IPNS isozymes reveal the complete conservation of two histidine (His214, His270), one aspartate (Asp216) [also known as the '2-His-l-carboxylate' motif] and one glutamine (Gln330) residue. The crystal structure of IPNS (Aspergillus nidulans) active site (in the absence of ACV) revealed an octahedrally coordinated manganese atom surrounded by these four protein ligands and two water molecules. The role of the four conserved metal binding ligands was investigated using site directed mutagenesis. The results demonstrated that ligation of the iron with Gln330 was not essential for the catalytic activity of IPNS. In contrast, ligation of the iron with the three remaining metal ligands was indispensable for catalytic activity. Additionally, it was demonstrated that the conserved Asp216 residue may be substituted by a glutamate residue (D216E) with significant retention of catalytic activity. Crystallographic and spectroscopic evidence suggested that the D216E mutant bound both iron and ACV in a similar way to wild-type IPNS. The inactivation of wild-type IPNS was examined under in vitro assay conditions. This study showed that inactivation of IPNS results (minimally) from a slow non-oxidative pathway (in buffer alone) and a fast oxidative pathway via Udenfriend's chemistry (ferrous iron, ascorbate, and oxygen). The oxidative inactivation pathway was substantially reduced by the inclusion of catalase in the assay mixture, thus indicating that oxidative IPNS inactivation results (in part) from the generation of hydrogen peroxide in solution. Inactivation was also accompanied by a slow fragmentation of intact IPNS into (at least) five oligopeptides (observed by sodium dodecyl sulphate polyacrylamide gel electrophoresis). N-Terminal sequencing analyses confirmed that the fragmentation resulted from at least two cleavage sites within the active site (between Asp216-Val217 and Val272-Lys273).

Planaria (class Turbellaria) are the highest life forms which exhibit fission (Hyman, 1951). The laboratory planarian, Dugesia, lives in lakes, ponds, streams and springs, where it occupies bottom habitats. Fissioning is an asexual mode of reproduction. The fission plane is usually transverse, forming behind the pharynx, and separation appears to be dependent upon locomotion (Curtis, 1902). The posterior half of the worm adheres to the substratum while the anterior half continues to move forward until the worm snaps in two. Each half then regenerates the missing parts, forming two new smaller worms.

Objectives: Rates of maternal syphilis have increased five-fold in Brazil in the past decade. While penicillin remains the only appropriate treatment for maternal syphilis, we hypothesized that low non-treponemal titers (<1:16) may lead to reduced penicillin treatment in Brazil. Methods: Using Brazilian Ministry of Health data on women diagnosed with maternal syphilis between January 1, 2010, and December 31, 2018, we conducted a random-effects logistic regression model with a cluster correction at the state level to evaluate predictive factors of penicillin treatment. Results: We observed yearly increases in cases of pregnant women with syphilis from 2010 to 2018. There was significant variation by state: 52,451 cases were reported in São Paulo, followed by 26,838 in Rio de Janeiro. Among 215,937 cases of maternal syphilis, 91·3% received penicillin. In the random-effects model, a non-treponemal titer ≥1:16 was associated with 1·44 higher odds of receiving penicillin (95% confidence interval [CI]: 1·391·48), and prenatal care was associated with a 2·12 increased odds of receiving penicillin (95% CI: 2·022·21). Although there is an association between the absence of prenatal care and inadequate treatment for syphilis, 83·2% of women in this cohort who did not receive penicillin were engaged in prenatal care. Conclusions: Providers may inappropriately exclude low non-treponemal titers and thereby fail to use penicillin treatment in maternal syphilis. While the cause of the maternal syphilis epidemic in Brazil is multifactorial, we believe our findings can be used to develop targeted interventions throughout Brazil as well as shape public health initiatives globally. / National Institute of Mental Health / Revisión por pares

Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Nutrition and Food Science, 1979. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND SCIENCE. / Vita. / Bibliography: leaves 296-304. / Ph.D.

A retrospective study (1990-1994) of the activities of ampicillin, unisyn, augmentin, ticarcillin, tinentin, piperacillin, and zosyn against several thousand isolates belonging to 8 species of bacteria (Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcensens, Morganella morganii, Proteus mirabilis, Pseudomonas aeruginosa and Staphylococcus aureus) in the Stockton area was reviewed. In addition, 233 isolates of the same species examined in 1994 were tested against the six penicillins and zosyn (in-house). The study shows that clavulanic acid 1 amoxicillin (Augmentin) combination has better activity than sulbactam 1 ampicillin combination (Unisyn) against E. coli, equal efficacy against K. pneumoniae, P. mirabilis, s. aureus but lesser active against E. cloacae, S. marcensens and ~ morganii. A comparison between the combination-drugs of clavulanic acidlticarcillin (Timentin) and tazobactaml piperacillin (Zosyn) generally indicates that they are equally effective on s. marcensens, M. morganii, ~ mirabilis, and s. aureus. Zosyn shows slightly better activity against E. coli, K. pneumoniae, E. cloacae, and ~ aeruginosa.

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This thesis discusses the development of penicillin during World War II, made possible by a complex relationship between private industry, academic researchers, and government research facilities and funding. It also examines the media response to the emergence of penicillin, the wide-spread war-time preoccupation with venereal disease, and the discovery of the potency of penicillin in treating such illnesses. It argues that the societal importance of penicillin was leveraged by policy makers in the post-war period to expand government funding for medical research and the role of the US Public Health Service. This was part of an overall trend of post-war expansion in government. / History