J. Baptista

Characterization of cytotoxic steroids in human faeces and their putative role in the etiology of human colonic cancer

It has been shown previously that chemically induced nuclear abeerrations in the murine colon are correlated with the carcinogenicity of the respective chemicals. Consequently, the nuclear aberration assay was utilized for the identification of putatife carcinogens in human faeces. Human fecal samples were fractionated by several chromatographic methods, and the assay led to the isolation of two substances. A combination of spectroscopic (mass, nuclear magnetic resonance, ultraviolet, and infrared) and chromatographic (HPLC and GLC) methods showed that they are 5-alpha- cholestan-3-one (I) and cholest-4-en-3-one (II). A number of C-27-C-30 steroids isolated from closely related fractions of feces were inactive in this assay. Thus I and II could play a role in etiology of large bowel cancer in humans.

On distribution of different fecapentaenes, the fecal mutagens, in the human population

It has been shown by an HPLC analysis using a quarternary solvent mixture in an isocratic mode that human excretors of these fecal mutagens excrete both fecapentaene -12 and -14 but the ratios vary greatly between individuals. Since these mutagens are produced by the bacterial flora of the colon, this may indicate differences in the flora between these individuals or differences in the availability of different precursor molecules in their colons. Any relationship of these findings to the etiology of colonic cancer is not clear.

Accessibility of D-Mannopyranoside Glycosylating Synthons by Acetolysis for Preparations of Oligosaccharide Moieties of N-Linked Glycoproteins

Abstract Selective acetolysis of methyl 2, 3, 4, 6-tetra-O-benzyl-α-D-manno-pyranoside (2) allows for easy preparation of 1-acetates of 2, 3,4, 6-tetra-O-benzyl (5), 6-O-acetyl-2, 3, 4, tri-O-benzyl-(6), 4, 6-di-O-acetyl-2,3-di-O-benzyl-(7), 3, 4, 6-tri-O-acetyl-2-O-benzyl-(8), and 2, 4, 6-tri-O-acetyl-3-O-benzyl-D-mannopyranoside (9). 8 and 9 formed are separated by preparative HPLC in 30-60g scale. The time course of previously described acetolyses of 3, 4, 6-tri-O-benzyl- 1, 2-O-(1-methoxyethyidene)-β-D-mannopyranose (3), and methyl 2, 3-dt-O-benzyl-4, 6-O-benzylldene-α-D-mannopyranoside (4) giving 9, 1, 2, 6-tri-O-acetyl-3, 4-di-O-benzyl-(10), and 1, 2-di-O-acetyl-3, 4, 6-tri-O-benzyl-(11) α-D-mannopyranose as well 7 have been studied.

The effect of fecapentaenes on nuclear aberrations in murine colonic epithelial cells

Fecapentaenes, human fecal mutagens of bacterial origin, were intrarectally administered to mice in suppository form. Despite the strong, positive mutagenic response of fecanpentaenes using Ames tester strains TA 98 and TA 100, no increase in nuclear aberrations, taken as a measure of genotoxicity in colonic epithelial cells, was observed over control levels. In fecapentaene treated animals, however, the incidence of mitotic figures was increased above control levels to values comparable to those observed in mice treated with the known colon carcinogen, N-ethyl-N-nitrosourea. Thus, it would appear that fecapentaenes are not cytotoxic to murine colonic epithelia as judged by the nuclear aberration assay.

Synthesis of L-Iduronic Acid Derivatives: Crystal Structure of Methyl (Methyl 2,3,4-Tri-O-Acetyl-β-L-Idopyranosid)Uronate

ABSTRACT Several L-iduronic acid derivatives were prepared by chemical synthesis including the reducing sugar, the α– and s-methyl glycosides and L-iduronolactone. The s-methyl glycoside, as well as two isomeric orthoesters, were the unexpected products of glycosylation of methyl (2,3,4-tri-O-acetyl-α-L-idopyranosyl bromide) uronate. EI-MS was used to distinguish between the orthoesters and the glycosides. The crystal structure of the s-methyl glycoside was determined by direct methods and refined by full-matrix least squares to a final value of R = 0.067 for 1739 reflections. The pyran ring was found to occur in the 1C4 conformation, with the three acetoxy substituents in axial orientations. In aqueous solution, the α-anomer of the reducing sodium salt is almost entirely in a 2SO ring conformation and the α-methyl glycoside is an equilibrium mixture of conformations which is sensitive to pH: The s-anomers all have spectral data consistent with predominant or only slightly distorted 1C4 chairs.

The involvement of dimethyl sulfoxide in a bacteriotoxic response of the Ames assay tester strains TA98 and TA100

Dimethyl sulfoxide is a widely accepted and recommended solvent in which to dissolve compounds to be tested for mutagenicity via the Ames Salmonella/mammalian microsome assay. Using tester strains TA98 and TA100, we observed a bacteriotoxic response with various fractions isolated from beer when dissolved in DMSO but not when dissolved in water. Further characterization of the role of solvent in simple model systems consisting of butanol, DMSO and bacteria strongly suggests a chemical reaction occurs between dimethyl sulfoxide and specific chemical constituents of the test substance, nutrient broth, or the Ames bacterial strains. The result of such an interaction could be misinterpreted as a toxic response to the test substance when, in fact, the bacteriotoxicity could be due to another compound, chemically distinct from the test substance.

Modification of a commercial preparative HPLC system allowing for UV detection of small amounts of materials with high extinction coefficients

SummaryA Waters Prep LC/System 500A was modified in order to allow separation of very small quantities of light-sensitive substances exhibiting very strong extinction coefficients (ε∼105) from large quantities of other materials.

Lipophilic substances in human faeces

plitude of head displacement is reached. Phasic discharge frequency within one cycle is related to frequency of sinusoidal head movement indicating a potential velocity sensitivity of the neck hair plates. The presence of both static and dynamic sensitivity has been demonstrated physiologically for neck hair plate sensilla in the honeybee [4] and trochanteral hair plate sensilla in the cockroach [5]. The primary afferents of the neck hair plate sensilla project into the prothoracic ganglion, where they show a complex, three-dimensional structure with ventral, dorsal, and latero-dorsal arborisations. A main bundle projects onto the mesothoracic ganglion. The dorsal arm of the hair plate sensilla projection shows an overlap with a neuropile area, which is occupied by neck muscle motoneurons. This overlap suggests functional connections between the two structures. In the locust neck hair plate projections make monosynaptic contacts with neck motoneurons [6]. The present study shows that both static position and movement of a mantids head are associated with appropriate patterns of nervous activity in neck proprioceptors, and that these inputs can modulate neck muscle motoneuron outputs.