Bactericidal activity of norfloxacin and nine other urinary tract antibiotics against Gram-negative bacilli causing bacteriuria in chronically catheterized patients

We compared the bactericidal activities of norfloxacin and nine other oral urinary tract antibiotics against 344 Gram-negative bacilli causing bacteriuria in chronically catheterized patients. Norfloxacin killed all organisms at 32 mg/l, 91% of isolates at 2 mg/l, and was the most active antibiotic tested.     

Attitudes to Sharing Personal Health Information in Living Kidney Donation

Background and objectives: In living kidney donation, transplant professionals consider the rights of a living kidney donor and recipient to keep their personal health information confidential and the need to disclose this information to the other for informed consent. In incompatible kidney exchange, personal health information from multiple living donors and recipients may affect decision making and outcomes.Design, setting, participants, & measurements: We conducted a survey to understand and compare the preferences of potential donors (n = 43), potential recipients (n = 73), and health professionals (n = 41) toward sharing personal health information (in total 157 individuals).Results: When considering traditional live-donor transplantation, donors and recipients generally agreed that a recipient''s health information should be shared with the donor (86 and 80%, respectively) and that a donor''s information should be shared with the recipient (97 and 89%, respectively). When considering incompatible kidney exchange, donors and recipients generally agreed that a recipient''s information should be shared with all donors and recipients involved in the transplant (85 and 85%, respectively) and that a donor''s information should also be shared with all involved (95 and 90%, respectively). These results were contrary to attitudes expressed by transplant professionals, who frequently disagreed about whether such information should be shared.Conclusions: Future policies and practice could facilitate greater sharing of personal health information in living kidney donation. This requires a consideration of which information is relevant, how to put it in context, and a plan to obtain consent from all concerned.Living kidney donation is a complex decision, with multiple medical, legal, and ethical facets. To proceed, transplant professionals discuss the risks and benefits with potential donors and recipients.Much of the information presented to potential living kidney donors and recipients is generic in nature (e.g., donor risk for perioperative death is 3/10,000 [1,2]); however, the transplant team may discover personal health information about a donor or a recipient that could affect expected outcomes. This information may be important to share so that informed decisions can be made about whether to proceed. Many regions have legislation that protects the confidentiality of personal health information (3–6); however, to satisfy the elements of informed consent, a person who is receiving treatment should also be provided with information that a reasonable person would want to know (7,8). For example, donors with mild controlled hypertension may be deemed eligible to donate by a transplant professional (9). Because the long-term medical outcomes for such donors are largely unknown (10,11), knowing this may alter a recipient''s willingness to accept the gift. A potential recipient who is HIV positive may be reluctant to divulge this information to their donor or family, which could alter the donor''s willingness to donate (12,13). In such situations, it is difficult to define which information is reasonable to share.To complicate the situation further, incompatible kidney exchanges have been introduced in many areas of the world, with national systems beginning in the United States in 2001 and Canada in 2009 (14,15). In this setting, multiple incompatible donor–recipient pairs are matched with each other to produce compatible matches, sometimes involving numerous pairs at multiple transplant centers, forming chains that can take months to complete (16). Donors and recipients are strangers to each other and may be more reluctant to share personal health information.These considerations prompted our examination of the preferences surrounding the sharing of personal health information in living kidney donation. There is no consensus on which information should be disclosed to all involved (17). In this study, we surveyed potential donors, potential recipients, and health professionals to understand better the attitudes toward sharing personal health information.     

Probing the bioactive constituents from chemotypes of the sponge Psammocinia aff. bulbosa

Since the report of (+)-psymberin (2) in 2004, many synthetic groups have pursued the synthesis of this compound, and our group has further collected Psammocinia aff. bulbosa to successfully isolate more 2. With more (+)-psymberin (2) in hand, additional clonogenic studies, a therapeutic efficacy assessment, and the hollow fiber assay have been completed. The inconsistent production of (+)-psymberin (2) and the classification of six Psammocinia species are further discussed herein. The most recent of these six collections resulted in the isolation of a new brominated cyclic peptide, (-)-psymbamide A (4), which is the first report of a Psammocinia-derived compound in this peptide class. The planar structure was solved via dereplication with Marinlit, HRESIMS, and 1D and 2D NMR techniques, and the absolute configuration determined using Marfey's method.     

Pinpointing pseurotins from a marine-derived Aspergillus as tools for chemical genetics using a synthetic lethality yeast screen

A new compound of mixed polyketide synthase-nonribosomal peptide synthetase (PKS/NRPS) origin, 11- O-methylpseurotin A ( 1), was identified from a marine-derived Aspergillus fumigatus. Bioassay-guided fractionation using a yeast halo assay with wild-type and cell cycle-related mutant strains of Saccharomyces cerevisiae resulted in the isolation of 1, which selectively inhibited a Hof1 deletion strain. Techniques including 1D and 2D NMR, HRESIMS, optical rotation, J-based analysis, and biosynthetic parallels were used in the elucidation of the planar structure and absolute configuration of 1. A related known compound, pseurotin A ( 2), was also isolated and found to be inactive in the yeast screen.     

Accelerating the discovery of biologically active small molecules using a high-throughput yeast halo assay

The budding yeast Saccharomyces cerevisiae, a powerful model system for the study of basic eukaryotic cell biology, has been used increasingly as a screening tool for the identification of bioactive small molecules. We have developed a novel yeast toxicity screen that is easily automated and compatible with high-throughput screening robotics. The new screen is quantitative and allows inhibitory potencies to be determined, since the diffusion of the sample provides a concentration gradient and a corresponding toxicity halo. The efficacy of this new screen was illustrated by testing materials including 3104 compounds from the NCI libraries, 167 marine sponge crude extracts, and 149 crude marine-derived fungal extracts. There were 46 active compounds among the NCI set. One very active extract was selected for bioactivity-guided fractionation, resulting in the identification of crambescidin 800 as a potent antifungal agent.     

Additional scalarane sesterterpenes from the sponge Phyllospongia papyracea

A chemical investigation of the marine sponge Phyllospongia papyracea, collected in Papua New Guinea, initiated by the screening result of a beta-catenin/Tcf4 disruption assay afforded six new bishomoscalarane sesterterpenes containing two rare scalaranes with a cyclobutane ring in the molecule, together with one known scalarane sesterterpene. The structures of the new compounds were elucidated by 1D and 2D spectroscopic techniques. The compounds isolated in this study did not show activity against the beta-catenin and Tcf4 complex.