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The aim of this study was to (1) determine if the organochlorine artificial sweetener sucralose is metabolized in rat intestine with repeated dosing and (2) examine whether sucralose might bioaccumulate in rat adipose tissue. Sucralose was administered to 10 rats by gavage daily for 40 days at an average dosage of 80.4 mg/kg/day. The dosages were within the range utilized in historical toxicology studies submitted for regulatory approval in North America, Europe, and Asia. Feces and urine were collected individually from each animal for every 24-hr period during the 40-day dosing period. Analysis of the urine and fecal extracts by ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) revealed two new biotransformation products that have not previously been reported. These two metabolites are both acetylated forms of sucralose that are less polar and hence more lipophilic than sucralose itself. These metabolites were present in urine and feces throughout the sucralose dosing period and still detected at low levels in the urine 11 days after discontinuation of sucralose administration and 6 days after sucralose was no longer detected in the urine or feces. The finding of acetylated sucralose metabolites in urine and feces do not support early metabolism studies, on which regulatory approval was based, that claimed ingested sucralose is excreted unchanged (i.e. not metabolized). The historical metabolic studies apparently failed to detect these metabolites in part because investigators used a methanol fraction from feces for analysis along with thin layer chromatography and a low-resolution linear radioactivity analyzer. Further, sucralose was found in adipose tissue in rats two weeks after cessation of the 40-day feeding period even though this compound had disappeared from the urine and feces. Thus, depuration of sucralose which accumulated in fatty tissue requires an extended period of time after discontinuation of chemical ingestion. These new findings of metabolism of sucralose in the gastrointestinal tract (GIT) and its accumulation in adipose tissue were not part of the original regulatory decision process for this agent and indicate that it now may be time to revisit the safety and regulatory status of this organochlorine artificial sweetener.

A status report of a program initiated in early 1981 to evaluate extracts of cultured blue-green algae for pharmacological activity and to isolate and identify active agents is presented. Novel macrolides and nucleosides, for example, have been shown to be responsible for the cytotoxic and fungicidal activities of many blue-green algae belonging to the Scytonemataceae. In the last two years this program has been expanded to include studies on marine animals that harbor symbiotic algae. Macrolides, for example, have been found to account for the potent cytotoxicity of an Indonesian sponge Hyattella sp. and a Guamanian tunicate Lissoclinum patella.

Sequencing amino acid units in peptides with molecular weights of 1000-2300 Da can be difhcult. The use of NOE-based experiments, for example, is frequently hampered by unfavorable rotational correlation times in this molecular weight range. The resulting lack of NOES between adjacent amino acid residues, coupled with the presence of nonsequential NOES in peptides due to intramolecularly hydrogenbonded amide groups, can sometimes lead to incorrect sequence assignments. Moreover, the use of long-range ‘H-13C or ‘H-j5N correlation experiments to sequence amino acid units through the amide carbonyls and nitrogens is often restricted by the combination of small coupling constants and short T2’s. The difficulties in using homonuclear and heteronuclear ‘H NMR techniques to sequence amino acids in smafl peptides have prompted us to devise a procedure on carbon-detected 13C-15N correlation spectroscopy. This experiment is of course difficult to perform at the natural abundance levels of r3C and “N. If the peptide is enriched with r5N to about 1570, however, sequencing can be achieved in a onedimensional experiment by correlating decoupled 13C signals in the carbony and a-methine regions with selectively irradiated 15N resonances. This approach has previously described by Llinas et al. (I). At 15N enrichment levels as low as 30-4096, two-dimensional correlation experiments become possible and in this report we describe our progress in examining the different approaches to this methodology. The logical first choice of experiments is an extension of the classical chemicalshift correlation (2). The basic pulse sequence is of the type

Die vorliegende Arbeit untersucht am Modell der Starkephagocytose den Einflus von Polyvinylpyrrolidon (PVP) und Dextran auf die Phagocytosetatigkeit der Leukocyten in vitro nach der Methode von v.Philipsborn undBucher in der Modifikation vonSiess.

Tubercidin, toyocamycin, and the corresponding 5'-alpha-D-glucopyranose derivatives of the nucleosides are frequently responsible for much of the cytotoxicity and antimycotic activity associated with extracts of cultured cyanophytes belonging to the family Scytonemataceae. The 5'-alpha-D-glucopyranoses of tubercidin and toyocamycin, for example, are the major cytotoxic and fungicidal nucleosides in Fijian Plectonema radiosum and Hawaiian Tolypothrix tenuis, respectively.

In seinen Arbeiten hat Schubert den Vorgang der Serum- und Gewebswasche durch Kollidon aufgezeigt. Damit ergab sich fur das Kollidon ein vollig neuartiges Indikationsgebiet, und heutigentages wird auf Grund dieses neuentwickelten Prinzips das Periston N, das als kolloidalen Bestandteil niedermolekulares Kollidon enthalt, in der Klinik bei einer Reihe von Infektionskrankheiten zur Entgiftung mit erwiesenem Erfolg angewandt. Gerade diese Anwendung last die Frage aufkommen, inwieweit hier die Leukocyten eine Abanderung ihrer phagocytierenden Eigenschaften erfahren.