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  • 1
    Language: English
    In: Journal of Physiology, March 1, 2014, Vol.592(5), p.1061(15)
    Description: To purchase or authenticate to the full-text of this article, please visit this link: http://onlinelibrary.wiley.com/doi/10.1113/jphysiol.2013.255687/abstract Byline: , , Bernardo Bollen Pinto, Bernadette O. Fernandez, Verena Simon, Martin Feelisch, Mervyn Singer Key points * Hypoxia increases blood flow through vasodilation, an adaptive response that increases oxygen availability to tissues. * This response is probably mediated by nitric oxide (NO); different mechanisms have been postulated (increased de novo synthesis, release from preformed stores, reduced inactivation), but precise mechanisms remain controversial. * In a short-term rodent model, hypoxaemia was associated with hypotension and lower plasma nitrite levels suggestive of nitrite bioactivation; this was only partially reversed by NO synthase inhibition. Administration of sodium nitrite produced marked vasodilation and increased nitrosylation. Scavenging of NO had little effect. * Early hypoxic vasodilation is mediated by a complex interaction of multiple NO-related species, rather than by NO from haemoglobin-mediated reduction of nitrite per se. * NO and its metabolites play a pivotal role in the body's initial adaptation to an acute decrease in oxygen supply, probably offering protection against a supply-demand mismatch. Abstract Local increases in blood flow - 'hypoxic vasodilation' - confer cellular protection in the face of reduced oxygen delivery. The physiological relevance of this response is well established, yet ongoing controversy surrounds its underlying mechanisms. We sought to confirm that early hypoxic vasodilation is a nitric oxide (NO)-mediated phenomenon and to study putative pathways for increased levels of NO, namely production from NO synthases, intravascular nitrite reduction, release from preformed stores and reduced deactivation by cytochrome c oxidase. Experiments were performed on spontaneously breathing, anaesthetized, male Wistar rats undergoing short-term systemic hypoxaemia, who received pharmacological inhibitors and activators of the various NO pathways. Arterial blood pressure, cardiac output, tissue oxygen tension and the circulating pool of NO metabolites (oxidation, nitrosation and nitrosylation products) were measured in plasma and erythrocytes. Hypoxaemia caused a rapid and sustained vasodilation, which was only partially reversed by non-selective NO synthase inhibition. This was associated with significantly lower plasma nitrite, and marginally elevated nitrate levels, suggestive of nitrite bioinactivation. Administration of sodium nitrite had little effect in normoxia, but produced significant vasodilation and increased nitrosylation during hypoxaemia that could not be reversed by NO scavenging. Methodological issues prevented assessment of the contribution, if any, of reduced deactivation of NO by cytochrome c oxidase. In conclusion, acute hypoxic vasodilation is an adaptive NO-mediated response conferred through bioactive metabolites rather than free NO from haemoglobin-mediated reduction of nitrite. Article Note: M. Umbrello and A. Dyson have contributed equally to this work. Supporting information: Additional Supporting Information may be found in the online version of this article CAPTION(S): Supporting Information
    Keywords: Cytochrome C -- Analysis ; Cytochrome Oxidase -- Analysis ; Nitric Oxide -- Analysis ; Metabolites -- Analysis ; Vasodilation -- Analysis ; Hemoglobins -- Analysis
    ISSN: 0022-3751
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  • 2
    In: Plant Journal, May 2013, Vol.74(4), pp.663-677
    Description: The transcription factor 16 (16) plays an important role in endothelial cell specification and proanthocyanidin () accumulation. However, its precise regulatory function with regard to the expression of endothelial‐associated genes in developing seeds, and especially in the ‐producing inner integument, remains largely unknown. Therefore, we endeavored to characterize four homologs from the allotetraploid oil crop species , and systematically explore their regulatory function in endothelial development. Our results indicated that all four genes were predominantly expressed in the early stages of seed development, but at distinct levels, and encoded functional proteins. interference lines exhibited abnormal endothelial development and decreased content, while polymerization was not affected. In addition to the previously reported function of 16 in the transcriptional regulation of () and (), we also determined that proteins played a significant role in the transcriptional regulation of five other genes involved in the biosynthetic pathway (〈0.01). Moreover, we identified two genes involved in inner integument development that were strongly regulated by the proteins ( and ). These results will better our understanding of the precise role of in endothelial development in rassicaceae species, and could potentially be used for the future improvement of oilseed crops.
    Keywords: Box Genes ; 16 ; Proanthocyanidin ; Seed Development ; Endothelium ; Genome Duplications
    ISSN: 0960-7412
    E-ISSN: 1365-313X
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  • 3
    Language: English
    In: Journal of Infectious Diseases, 2016, Vol.214(3), pp.489-495
    Keywords: Haemophilus Ducreyi ; Chancroid ; Skin Ulcers ; Immunogenetics ; Humans ; Innate Immunity
    ISSN: 0022-1899
    ISSN: 1537-6613
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  • 4
    In: The Journal of Infectious Diseases, 2016, Vol. 214(3), pp.489-495
    Description: Background.  In humans inoculated with Haemophilus ducreyi , there are host effects on the possible clinical outcomes—pustule formation versus spontaneous resolution of infection. However, the immunogenetic factors that influence these outcomes are unknown. Here we examined the role of 14 single-nucleotide polymorphisms (SNPs) in 7 selected pathogen-recognition pathways and cytokine genes on the gradated outcomes of experimental infection. Methods.  DNAs from 105 volunteers infected with H. ducreyi at 3 sites were genotyped for SNPs, using real-time polymerase chain reaction. The participants were classified into 2 cohorts, by race, and into 4 groups, based on whether they formed 0, 1, 2, or 3 pustules. χ 2 tests for trend and logistic regression analyses were performed on the data. Results.  In European Americans, the most significant findings were a protective association of the TLR9 +2848 GG genotype and a risk-enhancing association of the TLR9 TA haplotype with pustule formation; logistic regression showed a trend toward protection for the TLR9 +2848 GG genotype. In African Americans, logistic regression showed a protective effect for the IL10 – 2849 AA genotype and a risk-enhancing effect for the IL10 AAC haplotype. Conclusions.  Variations in TLR9 and IL10 are associated with the outcome of H. ducreyi infection.
    Keywords: 〈Kwd〉〈Italic Toggle="Yes"〉Haemophilus Ducreyi〈/Italic〉〈/Kwd〉 ; Chancroid ; Skin Ulcers ; Immunogenetics ; Humans ; Innate Immunity
    ISSN: 0022-1899
    E-ISSN: 1537-6613
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  • 5
    In: FEMS Pathogens and Disease, 2016, Vol. 74(2)
    Description: Bacterial urogenital infections such as chlamydia, gonorrhoea and syphilis are widespread inflammatory diseases, which may be accompanied by severe complications. These complications can range from basic inflammation to tubal pathology, infertility and neurological dysfunction, though infections go unnoticed in the majority of cases. Cytokines in the host play a vital role in both the initial and long-term immune response and inflammation. However, levels of cytokine expression vary between individuals. A meta-analysis was performed to evaluate the effect of cytokine expression differences on severity of infections with these pathogens. Studies comparing expression of cytokines in humans with inflammation or inflammation-based complications were identified using NCBI, Google Scholar and Cochrane databases. Only studies into human cytokine expressions were included, and three articles per subject were required to be suitably analysed during meta-analysis. A total of 52 articles were included for meta-analysis. It was shown that differences in IL-1, IL-6, IL-8, IL-10, TNFα and IFNγ affect the clinical outcome of Chlamydia trachomatis infection significantly. Similarly, IL-1 and IL-8 expression during Neisseria gonorrhoeae infection significantly affects the outcome of the disease. For Treponema pallidum infection, it was shown that IFNγ variation in hosts could be linked to severity of disease. However, a lack of studies to use in the meta-analysis and fluctuation in the resulting data depending on the adjustments makes adequate evaluation difficult. Analysis of articles on inflammation shows relations between secretion of inflammatory proteins and the severity of bacterial STD infection outcomes. Graphical Abstract Figure. Analysis of articles on inflammation shows relations between secretion of inflammatory proteins and the severity of bacterial STD infection outcomes.
    Keywords: 〈Kwd〉〈Italic Toggle="Yes"〉Chlamydia〈/Italic〉〈/Kwd〉 ; 〈Kwd〉〈Italic Toggle="Yes"〉Neisseria〈/Italic〉〈/Kwd〉 ; 〈Kwd〉〈Italic Toggle="Yes"〉Treponema〈/Italic〉〈/Kwd〉 ; Cytokine ; Profile ; Expression
    ISSN: 2049-632X
    E-ISSN: 2049-632X
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  • 6
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 13 March 2012, Vol.109(11), pp.4302-7
    Description: Gamma-band synchronization adjusts the timing of excitatory and inhibitory inputs to a neuron. Neurons in the visual cortex are selective for stimulus orientation because of dynamic interactions between excitatory and inhibitory inputs. We hypothesized that these interactions and hence also orientation selectivity vary during the gamma cycle. We determined for each spike its phase relative to the gamma cycle. As a function of gamma phase, we then determined spike rates and their orientation selectivity. Orientation selectivity was modulated by gamma phase. The firing rate of spiking activity that occurred close to a neuron's mean gamma phase of firing was most orientation selective. This stimulus-selective signal could best be conveyed to postsynaptic neurons if it were not corrupted by noise correlations. Noise correlations between firing rates were modulated by gamma phase such that they were not statistically detectable for the spiking activity occurring close to a neuron's mean gamma phase of firing. Thus, gamma-band synchronization produces spiking activity that carries maximal stimulus selectivity and minimal noise correlation in its firing rate, and at the same time synchronizes this spiking activity for maximal impact on postsynaptic targets.
    Keywords: Noise ; Cortical Synchronization -- Physiology ; Haplorhini -- Physiology ; Orientation -- Physiology ; Visual Cortex -- Physiology ; Wakefulness -- Physiology
    ISSN: 00278424
    E-ISSN: 1091-6490
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  • 7
    Language: English
    In: BMC infectious diseases, 16 July 2015, Vol.15, pp.273
    Description: Bacterial infections in the genital tract frequently result in morbidity through a variety of inflammation based symptoms. One component of the bacteria that may trigger host inflammatory response is their DNA. CpG motifs in this DNA are known targets for Toll-like receptor 9 (TLR9), which is a pathogen-recognition receptors focusing on CpG DNA. The activation of TLR9 induces the NF-κB inflammatory pathway. This study aims to provide a broad view of the inflammatory potential of CpG DNA motifs in bacteria related to genital diseases: C. trachomatis, E. coli, N. gonorrhoeae, G. vaginalis, H. ducreyi, L. crispatus, L. gasseri, M. hominis, M. genitalium, T. pallidum, and U. urealyticum. Publicly available genomic sequences of the bacterial species and strains have been analyzed in silico to produce a CpG index number. This CpG index number shows the relative inflammatory potential of the genome and has previously been used in a study by Lundberg et al. (2003). Higher CpG index values suggest a strong CpG induced inflammation potential during infection and vice versa. The highest observed CpG index belongs to G. vaginalis with a value of 26,2, suggesting a strong pro-inflammatory potential when in contact with TLR9. The lowest index belongs to N. gonorrhoeae with a value of -79,5, suggesting a strong immunoinhibitory effect on TLR9 contact. Interestingly, Lactobacilli showed a mean CpG index value of 4,2, suggesting a weak inflammatory potential. Our results show varying CpG index values between bacterial species. Comparison of CpG indices with the clinical course of several pathogens shows the CpG index helps clarify the clinical course of infection. However, we found no links between CpG index values and either obligate pathogenicity or facultative pathogenicity through bacterial vaginosis. Lactobacilli showed relatively low CpG indices which do suggest a lower inflammatory potential from these bacteria. Our results show varying CpG index values between bacterial species, which may help clarify the clinical course of infection, and may help diagnosis.
    Keywords: Bacteria -- Genetics ; DNA, Bacterial -- Chemistry ; Sexually Transmitted Diseases -- Microbiology
    E-ISSN: 1471-2334
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  • 8
    Language: English
    In: Journal of Neurology, Neurosurgery & Psychiatry, 21 September 2003, Vol.74(9), p.1299
    Description: The purpose of this study was to describe the process used to decide which patients are admitted to the intensive care unit (ICU) at a hospital with special focus on access for neurosurgery patients, and evaluate it using “accountability for reasonableness”.
    Keywords: Priority Setting ; Critical Care ; Neurosurgery
    ISSN: 0022-3050
    ISSN: 00223050
    E-ISSN: 1468-330X
    E-ISSN: 1468330X
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  • 9
    Language: English
    In: Parasitology Research, 2016, Vol.115(1), pp.329-337
    Description: Cryptosporidium is an important waterborne pathogen for which no treatment or vaccination is available. This study set out to quantify DNA replication of Cryptosporidium parvum in vitro. Cryptosporidium DNA could be detected at up to 60 % of input level in both host-cell-free and host cell containing cultures 6 days after infection with living sporozoites, but was lost within 2 days in cultures inoculated with UV-inactivated sporozoites. Total DNA increased between days 2 and 6, evidence of successful DNA replication in both cell-free and host-cell-containing cultures. Overall however, only a small fraction (up to 5 %) of parasite DNA could be found associated with host cells or bound to plastic of the cell-free cultures, and the majority of parasite DNA was present in the cell culture medium, separable by simple decantation. After 2 days, in host-cell-containing cultures, the parasite DNA could be concentrated by slow centrifugation, suggesting that it was associated with intact parasite cells, but at 6 days, the majority could not be centrifuged and is therefore thought to have represented copies associated with dead and degraded parasites. In cell-free cultures and in larger plates, the majority of DNA was in this form. Performance of the parasite was best in small culture plates, and least in the largest plate sizes. We interpret these results as suggesting that Cryptosporidium sporozoites first bind to the host cell monolayer or to the plasticware, but then by 2 days, there has been a substantial release of parasites back into the medium. Host-cell-free cultures also supported modest replication and may have represented DNA synthesis in cells beginning merogony. The role of the host cells is unclear, as so much of the parasite DNA is released into the medium. Host cells may provide a feeder role, conditioning the medium for Cryptosporidium development.
    Keywords: Cryptosporidium parvum ; HCT-8 human adenocarcinoma cells ; qPCR ; Host-cell-free culture
    ISSN: 0932-0113
    E-ISSN: 1432-1955
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  • 10
    Language: English
    In: Hand Surgery, 2013, Vol.18(2), pp.229-234
    Description: Purpose: The purpose of the study was to assess the efficacy of the conservative management of proximal phalangeal fractures in a dorsal plaster slab. Methods: Twenty-three consecutive patients with extra-articular proximal phalangeal fractures were included in this prospective study. Fourteen patients (62%) presented with fractures considered unstable. The fractures were reduced and the position was held with a dorsal plaster slab for three weeks. The patients were followed up for an average of seven weeks (range 2 to 45) after the injury. Range of motion of the finger and radiological evidence of union, non-union or malunion was documented after removal of the plaster. Results: Ninety-one percent of fractures maintained an acceptable reduction. All cases measured less than 15° of angulation. On average 1,1 mm of shortening was measured. In two (9%) cases the reduction was not accepted on follow up assessment and the fractures were managed surgically. Conclusion: Most extra-articular proximal phalanx fractures can be managed conservatively with acceptable results.
    Keywords: Proximal Phalanx ; Complex Finger Fractures ; Conservative Management ; Unstable Finger Fractures
    ISSN: 0218-8104
    E-ISSN: 1793-6535
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