Synthesis of isoindole and benzoisoindole derivatives of teicoplanin pseudoaglycon with remarkable antibacterial and antiviral activities

The primary amino function of teicoplanin pseudoaglycon has been transformed into arylthioisoindole or benzoisoindole and glycosylthioisoindole derivatives, in a reaction with o-phthalaldehyde or naphtalene-2,3-dicarbaldehyde and various thiols. All of the obtained semisynthetic antibiotics exhibited potent antibacterial activities against Gram-positive bacteria in the ng per ml concentration range. A few of them showed antiviral activity, in particular against influenza virus.     

The role of ABC-transporter gene polymorphisms in chemotherapy induced immunosuppression, a retrospective study in childhood acute lymphoblastic leukaemia

We examined the association of functional ABCB1 (MDR1) and ABCG2 (BCRP) polymorphisms with acute side effects of chemotherapy. Analyses were performed on clinical data from 138 patients treated with the ALL-BFM-95 protocol implying several substrates of these transporters. ABCB1 3435T>C, 2677G>T/A 1236C>T and ABCG2 421C>A genotypes were determined. A higher proportion of ABCB1 3435TT patients suffered excessive infectious complications than those harbouring at least one C allele (OR=2.5, p=0.03) during the whole half-year-long intensive phase of chemotherapy. Weaker associations were calculated when ABCB1 1236T-2677T-3435T haplotype homozygotes were tested against the remaining part of the population (OR=2.3, p=0.09). During the reinduction phase of therapy, the occurrence of severe leukocytopenia was similar among ABCB1 genotype groups. The frequency of any toxicities were not shown to differ according to the ABCG2 421C>A genotype. Our data suggest that the ABCB1 3435T>C genotype is associated with the infectious complications of the applied chemotherapy regimen.     

Epidemiology of Helicobacter pylori infection in the Czech Republic

BACKGROUND: Prevalence of Helicobacter pylori infection has been estimated to range from 60 to 95% in the former communist countries of Central and Eastern Europe. The aim of this study was to evaluate H. pylori infection prevalence in a representative sample of the Czech population. The second objective was to describe difference of H. pylori prevalence between different social groups of children and adults. MATERIALS AND METHODS: A total of 2509 persons aged 5-100 years, randomly selected out of 30,012 persons of the general population, took part in the study. H. pylori infection was investigated by means of 13C-urea breath test. Breath samples were analyzed by isotope ratio mass spectrometry. Social and demographic characteristics were based on data from self-completed questionnaires. RESULTS: Using the total Czech population as a standard, we estimated the age-standardized prevalence of H. pylori in males aged 5+ years at 41.9% (95% CI 39.0%, 44.8%) and in females aged 5+ years at 41.4% (95% CI 38.6%, 44.3%) in 2001. Prevalence of H. pylori increased with age but was not related to gender. Children of mothers with basic or lower education, living in crowded accommodations, without access to running warm water, and residing in smaller towns appear to be at the highest risk. Low education and heavy smoking are most strongly associated with prevalence of H. pylori positivity in adults and adolescents. CONCLUSIONS: This is a unique study based on a representative sample of the general population in a Central European country. The overall prevalence of H. pylori is lower than previously assumed and could partly reflect a substantial recent decrease in H. pylori prevalence in the Czech Republic. Consistent with earlier studies, H. pylori infection is strongly influenced by socioeconomic conditions and childhood poverty.     

No genetic bottleneck or associated microparasite loss in invasive populations of a freshwater amphipod

Understanding what factors determine the success of an invasive species in its adopted range is crucial from an evolutionary ecology point of view, because it can provide insights into which biological characteristics are required for survival in varied environmental conditions. Successful establishment may depend on both maintaining genetic diversity, which will allow the species to evolve and/or adapt to new environments, and the presence or absence of natural enemies such as parasites. We tested these two hypotheses by studying populations of the amphipod crustacean Dikerogammarus villosus . This Ponto-Caspian invader has rapidly and successfully invaded western Europe and threatens macroinvertebrate biodiversity in its adopted ranges. It is a unique system to study since both its colonisation history and its geographic origins are well-known. Using samples from the whole geographic range of the invasion route, and using four molecular markers, we found no evidence for genetic bottlenecks during the invasion of D. villosus in western Europe, despite slight variations in allelic proportions according to spatio-temporal subdivisions of our dataset. In addition, we analysed the prevalence and diversity of parasites across its native and adopted range. We found no macro-parasites, and no significant parasite loss of microsporidian parasites during the invasive process. Our data suggest that D. villosus invasion was either massive, or recurrent, or both, allowing a parasitic cortege to follow the host. The maintenance of genetic diversity may have contributed to its success, including the variation in resistance in the face of the natural enemies.     

The Murine Nucleolin Protein Is an Inducible DNA and ATP Binding Protein Which Is Readily Detected in Nuclear Extracts of Lipopolysaccharide-Treated Splenocytes

A 100-kDa DNA binding protein was found to be dramatically up-regulated upon the mitogenic stimulation of murine splenocytes with bacterial lipopolysaccharide (LPS). The induced DNA binding protein was also found to exhibit moderate binding specificity for the immunoglobulin isotype switch DNA repeats. Furthermore, the induction of the 100-kDa protein by LPS was found to be mediated by both an increase in the protein's stability and an increase in the synthesis of the protein. In vitro phosphorylation experiments revealed that the 100-kDa DNA binding protein was one of the most heavily phosphorylated proteins in both lymphoid and nonlymphoid nuclear extracts. Although this in vitro phosphorylation initially appeared to be mediated by a potent nuclear kinase activity, it was later determined that a significant part of the detected labeling was due to the direct binding of ATP by the 100-kDa protein. Antibodies raised to the 100-kDa DNA binding protein were used to isolate cDNA clones from a lymphocyte cDNA λgt11 expression library. Nucleotide sequence analysis revealed that the cloned cDNAs were identical to the mouse nucleolin gene. The β-galactosidase fusion proteins (encoded by exons 3-14 of nucleolin) and a more severely truncated 45-kDa protein (encoded by exons 5-14 of nucleolin) were both found to bind strongly to DNA and ATP. Furthermore, the strength of DNA binding was found to be highly dependent on the overall dG content of the DNA probes. Our experiments also revealed that apart from binding ATP and G-rich DNA, nucleolin directly bound GTP, dATP, and dGTP, but not dCTP, dTTP, or dUTP. Computer analysis revealed that the putative ATP binding domains appear to fall within two of the phylogenetically conserved RNA binding domains of nucleolin.     

Occurrence of ethanol in pea plants in the course of growth under normal and anaerobic conditions

1. At a so-called natural anaerobiosis during the first 48 hours of germination the concentration of ethanol in pea tissues increases (according to the cultivation conditions) up to 40 μmol per gram fresh weight.
2. In a nitrogen atmosphere the content of ethanol in pea seedlings increases as well, and after a 90 hour incubation in N₂ it can reach even 100 μmol ethanol per gram fresh weight. In older plants the content increases the most markedly in cotyledons, but considerable amounts were revealed also in stems and roots. Its increase in vegetative organs of plants cultivated both in light and darkness is more or less identical. Ethylalcohol can be formed by the vegetative organs themselves, as proved by the increase of this metabolite in plants deprived of reserve organs; in addition, however, it is evidently transported into them from reserve parts. Ethanol formed under anaerobiosis is catabolyzed after transferring plants to the air.

     

Enhanced vascular permeability facilitates entry of plasma HDL and promotes macrophage-reverse cholesterol transport from skin in mice

Reverse cholesterol transport (RCT) pathway from macrophage foam cells initiates when HDL particles cross the endothelium, enter the interstitial fluid, and induce cholesterol efflux from these cells. We injected [³H]cholesterol-loaded J774 macrophages into the dorsal skin of mice and measured the transfer of macrophage-derived [³H]cholesterol to feces [macrophage-RCT (m-RCT)]. Injection of histamine to the macrophage injection site increased locally vascular permeability, enhanced influx of intravenously administered HDL, and stimulated m-RCT from the histamine-treated site. The stimulatory effect of histamine on m-RCT was abolished by prior administration of histamine H1 receptor (H1R) antagonist pyrilamine, indicating that the histamine effect was H1R-dependent. Subcutaneous administration of two other vasoactive mediators, serotonin or bradykinin, and activation of skin mast cells to secrete histamine and other vasoactive compounds also stimulated m-RCT. None of the studied vasoactive mediators affected serum HDL levels or the cholesterol-releasing ability of J774 macrophages in culture, indicating that acceleration of m-RCT was solely due to increased availability of cholesterol acceptors in skin. We conclude that disruption of the endothelial barrier by vasoactive compounds enhances the passage of HDL into interstitial fluid and increases the rate of RCT from peripheral macrophage foam cells, which reveals a novel tissue cholesterol-regulating function of these compounds.