Search Results

You are looking at 1 - 10 of 15 items for

  • Author or Editor: André Fischer x
  • Refine by Access: All Content x
Clear All Modify Search

Abstract  

As a corollary of former studies, high performance in Brazilian Management Sciences during the period of 1981 to 1995 is put to scrutiny. Information on the 66 papers registered to this field in the ISI databases for this time interval were retrieved, edited and processed as to elicit patterns.Occurrences of highly cited papers seemed haphazard but the presence of collaborative work consistently emerged as an important driving factor for good performance. International collaboration showed the most expressive impact over chances of citation but any form of collaboration seemed to have some effect, even those represented by single authors with double allegiance. Simple addition of authors, nonetheless, had no effect, and thus collaboration involving authors of common institutional affiliation showed the performance of single authored papers.Cluster analysis allowed the identification of patterns of performance, and groups of best performers showed higher levels of international collaboration. The institutional composition of the clusters is presented.

Restricted access

The resistance of commensal bacteria to first and second line antibiotics has reached an alarming level in many parts of the world and endangers the effective treatment of infectious diseases. In this study, the influence of the plant-derived natural saponins glycyrrhizic acid, β-aescin, α-hederin, hederacoside C, and primulic acid 1 on the susceptibility of vancomycin-resistant enterococci (VRE) against antibiotics of clinical relevance was investigated in 20 clinical isolates. Furthermore, the antibacterial properties of saponins under study against VRE were determined in vitro. Results reveal that the susceptibility of VRE against gentamicin, teicoplanin, and daptomycin was enhanced in the presence of the saponin glycyrrhizic acid. Most importantly, glycyrrhizic acid (1 mg/ml) diminished the minimal inhibitory concentration (MIC) of gentamicin in gentamicin low-level intrinsic resistant VRE from 2 − >8 mg/l to ≤ 0.125−1 mg/l. The adding of β-aescin, α-hederin, hederacoside C, and primulic acid 1 to the antibiotics under study showed, compared to glycyrrhizic acid, less influence on the antibiotic potency. Only glycyrrhizic acid (1 mg/ml) and α-hederin (0.2 mg/ml) showed weak antibacterial properties against the clinical isolates. Our study points towards a therapeutic potential of saponins in the coapplication with antibiotics for bacterial infections.

Open access
European Journal of Microbiology and Immunology
Authors: Kerstin A. Heyl, André Fischer, Ulf B. Göbel, Peter Henklein, Markus M. Heimesaat, and Stefan Bereswill

Abstract

Helicobacter pylori infection is the most common cause of gastroduodenal ulcerations worldwide. Adaptation of H. pylori to the acidic environment is mediated by urease splitting urea into carbon dioxide and ammonia. Whereas neutralization of acid by ammonia is essential for gastric H. pylori colonization, the catalytic activity of urease is mediated by nickel ions. Therefore, nickel uptake and metabolism play key roles in H. pylori infection and urease is considered first line target for drug development and vaccination. Since nickel binding within H. pylori cells is mediated by the Histidine-rich protein designated Hpn, we investigated whether nickel binding by a synthetic Hpn is capable of abrogating urease activity of live H. pylori in liquid cultures. Supplementation of growth media with synthetic Hpn completely inhibited urease acitivity in live cells, indicating that H. pylori nickel uptake is effectively blocked by Hpn. Thus, nickel chelation by Hpn is stronger than nickel uptake of H. pylori offering therapeutic use of Hpn. Although the nickel binding of Hpn was confirmed by binding assays in vitro, its use in anti-H. pylori directed strategy will further need to be adapted to the gastric environment given that protons interfere with nickel binding and Hpn is degraded by pepsin.

Restricted access

Within 1 week following peroral Campylobacter jejuni infection, infant mice develop acute enteritis resolving thereafter. We here assessed colonic expression profiles of mediators belonging to the IL-23/IL-22/IL-18 axis and of matrix-degrading gelatinases MMP-2 and MMP-9 at day 6 post C. jejuni strain 81-176 infection. Whereas the pathogen readily colonized the intestines of infant IL-18−/− mice only, colonic mucin-2 mRNA, a pivotal mucus constituent, was downregulated in IL-22−/− mice and accompanied by increased expression of pro-inflammatory cytokines including IFN-γ, TNF, IL-17A, and IL-1β. Furthermore, in both naive and infected IL-22−/− mice, colonic expression of IL-23p19 and IL-18 was lower as compared to wildtype mice, whereas, conversely, colonic IL-22 mRNA levels were lower in IL-18−/− and colonic IL-18 expression lower in IL-23p19−/− as compared to wildtype mice. Moreover, colonic expression of MMP-2 and MMP-9 and their endogenous inhibitor TIMP-1 were lower in IL-22−/− as compared to wildtype mice at day 6 postinfection. In conclusion, mediators belonging of the IL-23/IL-22/IL-18 axis as well as the gelatinases MMP-2 and MMP-9 are involved in mediating campylobacteriosis of infant mice in a differentially regulated fashion.

Open access

Host immune responses are crucial for combating enteropathogenic infections including Campylobacter jejuni. Within 1 week following peroral C. jejuni infection, secondary abiotic IL-10−/− mice develop severe immunopathological sequelae affecting the colon (ulcerative enterocolitis). In the present study, we addressed whether pathogen-induced pro-inflammatory immune responses could also be observed in the small intestines dependent on the innate receptor nucleotide-oligomerization-domain-protein 2 (Nod2). Within 7 days following peroral infection, C. jejuni stably colonized the gastrointestinal tract of both IL-10−/− mice lacking Nod2 (Nod2−/− IL-10−/−) and IL-10−/− controls displaying bloody diarrhea with similar frequencies. Numbers of apoptotic and regenerating epithelial cells increased in the small intestines of C. jejuni-infected mice of either genotype that were accompanied by elevated ileal T and B lymphocyte counts. Notably, ileal T cell numbers were higher in C. jejuni-infected Nod2−/− IL-10−/− as compared to IL-10−/− counterparts. Furthermore, multifold increased concentrations of pro-inflammatory cytokines including IFN-γ, TNF, and MCP-1 could be measured in small intestinal ex vivo biopsies derived from C. jejuni-infected mice of either genotype. In conclusion, C. jejuni-induced pro-inflammatory immune responses affected the small intestines of both Nod2−/− IL-10−/− and IL-10−/− mice, whereas ileal T lymphocyte numbers were even higher in the former.

Open access

Host immune responses are pivotal for combating enteropathogenic infections. We here assessed the impact of the innate receptor nucleotide oligomerization domain protein 2 (NOD2) in murine Campylobacter jejuni-infection. Conventionally colonized IL-10−/− mice lacking NOD2 and IL-10−/− controls were perorally challenged with C. jejuni strain 81-176 and displayed comparable pathogenic colonization of intestines until day 14 postinfection (p.i.). Whereas overall intestinal microbiota compositions were comparable in naive mice, NOD2−/− IL-10−/− mice exhibited less fecal bifidobacteria and lactobacilli than IL-10−/− counterparts after infection. Interestingly, NOD2−/− IL-10−/− mice were clinically more compromised during the early phase of infection, whereas, conversely, IL-10−/− animals exhibited more frequently bloody feces lateron. While colonic apoptotic cell and T lymphocyte numbers were comparable in either C. jejuni-infected mice, B lymphocytes were lower in the colon of infected NOD2−/− IL-10−/− mice versus controls. At day 14 p.i., colonic TNF and IL-23p19 mRNA levels were upregulated in NOD2−/− IL-10−/− mice only. Translocation rates of intestinal commensals to mesenteric lymphnodes and extra-intestinal compartments including liver and kidney were comparable, whereas viable bacteria were more frequently detected in spleens derived from IL-10−/− as compared to NOD2−/− IL-10−/− mice. In conclusion, NOD2 is involved during C. jejuni infection in conventionally colonized IL-10−/− mice in a time-dependent manner.

Open access

Arcobacter butzleri causes sporadic cases of gastroenteritis, but the underlying immunopathological mechanisms of infection are unknown. We have recently demonstrated that A. butzleri-infected gnotobiotic IL-10−/− mice were clinically unaffected but exhibited intestinal and systemic inflammatory immune responses. For the first time, we here investigated the role of Toll-like receptor (TLR)-4, the main receptor for lipopolysaccharide and lipooligosaccharide of Gram-negative bacteria, in murine arcobacteriosis. Gnotobiotic TLR-4/IL-10-double deficient (TLR-4−/− IL-10−/−) and IL-10−/− control mice generated by broad-spectrum antibiotics were perorally infected with A. butzleri. Until day 16 postinfection, mice of either genotype were stably colonized with the pathogen, but fecal bacterial loads were approximately 0.5–2.0 log lower in TLR-4−/− IL-10−/− as compared to IL-10−/− mice. A. butzleri-infected TLR-4−/− IL-10−/− mice displayed less pronounced colonic apoptosis accompanied by lower numbers of macrophages and monocytes, T lymphocytes, regulatory T-cells, and B lymphocytes within the colonic mucosa and lamina propria as compared to IL-10−/− mice. Furthermore, colonic concentrations of nitric oxide, TNF, IL-6, MCP-1, and, remarkably, IFN and IL-12p70 serum levels were lower in A. butzleri-infected TLR-4−/− IL-10−/− versus IL-10−/− mice. In conclusion, TLR-4 is involved in mediating murine A. butzleri infection. Further studies are needed to investigate the molecular mechanisms underlying Arcobacter—host interactions in more detail.

Open access
European Journal of Microbiology and Immunology
Authors: Markus M. Heimesaat, Gül Karadas, André Fischer, Ulf B. Göbel, Thomas Alter, Stefan Bereswill, and Greta Gölz

Sporadic cases of gastroenteritis have been attributed to Arcobacter butzleri infection, but information about the underlying immunopathological mechanisms is scarce. We have recently shown that experimental A. butzleri infection induces intestinal, extraintestinal and systemic immune responses in gnotobiotic IL-10−/− mice. The aim of the present study was to investigate the immunopathological role of Toll-like Receptor-4, the receptor for lipopolysaccharide and lipooligosaccharide of Gram-negative bacteria, during murine A. butzleri infection. To address this, gnotobiotic IL-10−/− mice lacking TLR-4 were generated by broadspectrum antibiotic treatment and perorally infected with two different A. butzleri strains isolated from a patient (CCUG 30485) or fresh chicken meat (C1), respectively. Bacteria of either strain stably colonized the ilea of mice irrespective of their genotype at days 6 and 16 postinfection. As compared to IL-10−/− control animals, TLR-4−/− IL-10−/− mice were protected from A. butzleri-induced ileal apoptosis, from ileal influx of adaptive immune cells including T lymphocytes, regulatory T-cells and B lymphocytes, and from increased ileal IFN secretion. Given that TLR-4-signaling is essential for A. butzleri-induced intestinal inflammation, we conclude that bacterial lipooligosaccharide or lipopolysaccharide compounds aggravate intestinal inflammation and may thus represent major virulence factors of Arcobacter. Future studies need to further unravel the molecular mechanisms of TLR-4-mediated A. butzleri-host interactions.

Open access
European Journal of Microbiology and Immunology
Authors: Markus M. Heimesaat, André Fischer, Anja A. Kühl, Ulf B. Göbel, Illana Gozes, and Stefan Bereswill

The octapeptide NAP has been shown to exert neuroprotective properties. Here, we investigated potential anti-inflammatory effects of NAP in an acute ileitis model. To address this, C57BL/6j mice were perorally infected with Toxoplasma gondii (day 0). Within 1 week postinfection (p.i.), placebo (PLC)-treated mice developed acute ileitis due to Th1-type immune responses. Mice that were subjected to intraperitoneal NAP treatment from day 1 until day 6 p.i., however, developed less distinct macroscopic and microscopic disease as indicated by less body weight loss, less distinct histopathological ileal changes, and lower ileal apoptotic, but higher proliferating cell numbers, less abundance of neutrophils, macrophages, monocytes, and T lymphocytes, but higher numbers of regulatory T cells in the ileal mucosa and lamina propria, and lower concentrations of pro-inflammatory mediators in the ilea as compared to PLC controls at day 7 p.i. Remarkably, NAP-mediated anti-inflammatory effects could also be observed in extra-intestinal compartments including liver and spleen. Strikingly, lower MCP-1, TNF, and IL-12p70 serum concentrations in NAP as compared to PLC-treated mice at day 7 p.i. indicate a pronounced systemic anti-inflammatory effect of NAP in acute ileitis. These findings provide first evidence for NAP as a potential novel treatment option in intestinal inflammation.

Open access
European Journal of Microbiology and Immunology
Authors: Markus M. Heimesaat, Marie E. Alutis, Ursula Grundmann, André Fischer, Ulf B. Göbel, and Stefan Bereswill

We have recently shown that, within 1 week following peroral Campylobacter jejuni infection, conventional infant mice develop self-limiting enteritis. We here investigated the role of IL-23, IL-22, and IL-18 during C. jejuni strain 81-176 infection of infant mice. The pathogen efficiently colonized the intestines of IL-18−/− mice only, but did not translocate to extra-intestinal compartments. At day 13 postinfection (p.i.), IL-22−/− mice displayed lower colonic epithelial apoptotic cell numbers as compared to wildtype mice, whereas, conversely, colonic proliferating cells increased in infected IL-22−/− and IL-18−/− mice. At day 6 p.i., increases in neutrophils, T and B lymphocytes were less pronounced in gene-deficient mice, whereas regulatory T cell numbers were lower in IL-23p19−/− and IL-22−/− as compared to wildtype mice, which was accompanied by increased colonic IL-10 levels in the latter. Until then, colonic pro-inflammatory cytokines including TNF, IFN-γ, IL-6, and MCP-1 increased in IL-23p19−/− mice, whereas IL-18−/− mice exhibited decreased cytokine levels and lower colonic numbers of T and B cell as well as of neutrophils, macrophages, and monocytes as compared to wildtype controls. In conclusion, IL-23, IL-22, and IL-18 are differentially involved in mediating C. jejuni-induced immunopathology of conventional infant mice.

Open access