Intestinal first-pass metabolism of nitrosamines. 2. Metabolism of N-nitrosodibutylamine in isolated perfused rat small intestinal segments

In a previous study a high first-pass metabolism of N-nitrosodi-[1-¹⁴C]butylamine(NDBA, O.32–730p.µM) has been shown in isolatedperfused rat small intestinal segments. In the present workthe identification and quantitation of metabolitesin samplesof perfusate and absorbed fluid (absorbate) is reported. AfterHPLC enrichment and purification five metabolites could be identifiedby GLC-MS: N-nitrosobutyl-(3-hydroxybutyl)amine (NB3HBA), N-nitrosobutyl-(4-hydroxybutyl)amine(NB4HBA), N-nitrosobutyl-(3-carboxypropyl)amine (NB3CPA), N-nitrosobutyl-(2-hydroxy-3-carboxypropyl)amine(NB2H3CPA) and N-nitrosobutylcarboxymethylamine (NBCMA), representing> 95% of total metabolites. -hydroxylatlon leading to NB4HBAand NB3CPA accounted for 75–95% of total metabolites.The formation of their follow-up products NB2H3CPA and NBCMAwas too small for quantitative analysis. In absorbate NB3CPAwas by far the most important metabolite. The hydroxylationof NB4HBA to NB3CPA was more efficient in jejunal as comparedto ileal segments.-1-hydroxylation to NB3HBA and, as reportedpreviously, -hydroxylation were only minor metabolic pathways.In conclusion, a high first-pass metabolism of NDBA to the proximatebladder carcinogen NB3CPA takes place during its absorptionin rat small intestine. This is in contrast to the observationin rat liver preparations, where - and -1-hydroxylation arethe predominant pathways. The intestinal first-pass metabolismmay play a key role explaining the increased incidence of bladdertumors in rats after low oral doses of NDBA.     

Zum Reaktionsmechanismus der Oxygenierung von Naphtholen mit dem System CuCl/O2

Mechanism of the CuCl/O₂-mediated Oxygenation of Naphtholes The mechanism of the oxygenation of 1- and 2-naphthole derivatives in the system $\left[ {\mathop {\rm C}\limits^{+} \mathop {\rm u}\limits^{1} {\rm L}_4 } \right]^{+} + {\rm O}_2 \rightleftharpoons \left[ {\mathop {\rm C}\limits^{+} \mathop {\rm u}\limits^2 {\rm L}_3 {\rm O}_2^{^.} } \right]^{+} + {\rm L}$ depending on solvent (L) and temp., is studied. It was possible to distinguish between reactions via the radical ion pair type (L = CH₃CN) and hydrogen abstraction via free radicals (L = CH₃OH). There is a marked difference between the oxygen transfer to the naphthole derivatives and the oxygenation of 2, 6-di-tert.-butylphenol ( 6 ), which does not depend characteristically on L and temp.     

Impaired tactile pattern recognition in the early stage of primary degenerative dementia compared with normal aging

Tactile pattern recognition of ten different patterns which were engraved upon 4 x 4 cm plastic plaquettes with one hand and thereafter drawing with the other or the same hand was tested in 21 patients with a mild stage primary degenerative presenile onset dementia of Alzheimer type (DAT) and in 14 patients with a questionable dementia on the background of a chronic cardiovascular disease (CVD) in comparison to 15 healthy subjects of the same age (51 years old, elder controls, (EC)) and 16 younger subjects (22 years old, younger controls, (YC)). Patients made about four times more errors than the EC group. Duration from the begin of touching to the end of drawing was significantly longer in patients than in controls. In a second task the subjects had to recognize four subsequent patterns, then to perform a standard multiplication task and afterwards to draw all four patterns in their correct sequence. Patients made about ten times more errors in pattern recognition and series reproduction than age-matched controls.     

Decrease of elastic tissue fibres in stem villus blood vessels of the human placenta during IUGR and IUGR with concomitant pre-eclampsia

In a recent study we described an increase of elastic tissue fibres in blood vessel walls of placental stem villi during pre-eclampsia when compared to uncomplicated pregnancies. Furthermore, the thickness of these blood vessel walls was enhanced in pre-eclampsia. Since it is known that elastic tissue fibres increase in systemic hypertension, it may be assumed that the enhancement of elastic tissue fibres in placental stem villi during pre-eclampsia may be induced by the hypertension. To get further insight into this assumption, we examined the amount of elastic tissue fibres in stem villus blood vessels of placentae of pregnancies complicated by intrauterine growth retardation (isolated IUGR, fourteen cases), a disease without hypertension of the mother and such with pre-eclampsia and concomitant IUGR (IUGR+PE, nine cases). Each study group was compared with uncomplicated pregnancies (twenty-six cases). Unfixed cryostat serial sections were processed for conventional orcein staining and for the demonstration of alpha-actin-immunoreactivity. The intensity of orcein staining of stem villus blood vessel walls was evaluated by a semiquantitative score method. Significant lower intensities of orcein staining were calculated for blood vessel walls of placentae of isolated IUGR (P=0.0007) and IUGR+PE (P=0.0039) when compared to uncomplicated pregnancies each. Additionally, the blood vessel wall thickness of stem villi of isolated IUGR (P=0.0081) and IUGR+PE (P=0.0007) was significantly reduced. In comparison to the above mentioned investigation, our results show that, in contrast to isolated pre-eclampsia, elastic tissue fibres are decreased during pregnancies complicated by IUGR, independently of the occurrence of concomitant pre-eclampsia when compared to uncomplicated pregnancies. From our studies it may be considered that the increase of elastic tissue fibres in placentae of patients with isolated pre-eclampsia may be induced by systemic hypertension. Furthermore, our study underline arguments that IUGR may be an independent disease of the fetus.     

Taste bud development in the zebrafish, Danio rerio.

Taste buds are chemosensory endorgans consisting of modified epithelial cells. Fish and other vertebrates use their taste bud cells to sample potential food, either selecting or rejecting substances according to their edibility. The adult gustatory system in fish has been studied thoroughly, including regeneration experiments. Taste buds occur in the epithelia of the lips, the mouth cavity, the oropharyngeal cavity, and also in the skin of the barbels, the head, and sometimes even all over the body surface. Despite its importance for feeding, little is known about the ontogeny of the fish taste system. We examined the development of taste buds in the zebrafish on the light microscopical and the scanning and transmission electron microscopical levels. Taste buds develop later than the olfactory organ and the solitary chemosensory cells, two other chemosensory systems in aquatic vertebrates. The first few taste bud primordia are visible within the epithelia of lips and gill arches 3 to 4 days after fertilization, and the first few taste buds with open receptor areas appear on the lips and simultaneously on the gill arches 4-5 days after fertilization, which coincides with the onset of feeding. Taste buds in the mouth cavity, on the head, and on the barbels are formed later in development. As seen in other fish, zebrafish taste buds contain elongate dark and light cells, termed according to their electron density. Dark cells with a cell apex of many short microvilli appear first, followed by the light cells with one large microvillus. In addition, the zebrafish has a third fusiform cell type, which appears last. This cell type is low in electron density and has a brush-like apical ending with several small microvilli. This cell type has not been described previously. Furthermore, in zebrafish, the ontogenetic processes of taste bud formation differ from regenerative processes described in the literature.     

Intermediate filament expression in human vascular smooth muscle and in arteriosclerotic plaques

Summary Different regions of human aorta and of other human arteries obtained at autopsy were analyzed with regard to their topography and to the different stages of arteriosclerosis. Material was studied by immunocytochemical techniques with antibodies specific for either desmin (D) or for vimentin (V), the two types of intermediate filament proteins present in vascular smooth muscle cells. In normal arteries endothelial cells as well as the adjacent intimal cells were D–V+. In the media D+V+ as well as D–V+ cells were present, with the relative numbers of each cell type dependent on the particular blood vessel. When cells in arteriosclerotic plaques at different stages of development were examined an occasional plaque showed cells of the D+V+ type. In the majority of plaques however the cells were V– D+. In plaques where severe ulceration and necrotic material was present D–V+ cells were found at the border of the lesion: foam cells when they could be identified appeared to be D–V+.     

Innate recognition of bacteria: engagement of multiple receptors

Until recently, consensus was that the mechanism of action of the innate immune system was a simplified one. Current research findings in the field of innate recognition of bacteria suggest that it involves complex associations of receptors depending on cell type and bacterial stimuli, CD14, integrins, Toll-like receptors (TLRs), CD55, ion channels, and activation clusters containing heat shock proteins, chemokine receptor 4 and a plethora of other molecules have been shown to serve as key molecules in bacterial recognition. In this article, we review all the advances in the field and discuss the possibility that the repertoire for recognition of pathogens is defined by the combinational engagement of multiple receptors.