62 research outputs found
The Effect of stem cell mobilisation with granulocyte colony-stimulating factor on the morphology of the haematopoietic organs in mice
The cellular mobilisation of mice with granulocyte colony-stimulating factor
(G-CSF) results in an egress of haematopoietic stem/progenitor cells from the bone marrow and an increase in their level in the peripheral blood. While the mobilisation process with different agents is widely studied, little is known about the morphology of the murine haematopoietic organs during the mobilisation. The purpose of this study was to examine the morphology of the bone marrow, spleen and liver in mice mobilised with G-CSF. To address this issue mice were injected subcutaneously with G-CSF for 6 consecutive days. Morphological analysis
revealed an increase in the number of mature neutrophils close to the wall
of sinusoids in the bone marrow as well as hypertrophy of the red pulp in the
spleen. At the same time no morphological changes were noticed in the livers of G-CSF-mobilised mice. In conclusion, G-CSF induces discrete ultrastructural changes in the bone marrow, which intensify the transendothelial traverse of haematopoietic stem and progenitor cells from it. The changes in the spleen are
related to repopulation of this organ by mobilised early haematopoietic cells
circulating in the peripheral blood. We also noticed that the process of migration of haematopoietic cells from the bone marrow into the peripheral blood began on day 2 and was most pronounced on day 4 after stimulation with G-CSF
Remodeling of the Streptococcus agalactiae Transcriptome in Response to Growth Temperature
BACKGROUND: To act as a commensal bacterium and a pathogen in humans and animals, Streptococcus agalactiae (group B streptococcus, GBS) must be able to monitor and adapt to different environmental conditions. Temperature variation is a one of the most commonly encountered variables. METHODOLOGY/PRINCIPAL FINDINGS: To understand the extent to which GBS modify gene expression in response to temperatures encountered in the various hosts, we conducted a whole genome transcriptome analysis of organisms grown at 30 degrees C and 40 degrees C. We identified extensive transcriptome remodeling at various stages of growth, especially in the stationary phase (significant transcript changes occurred for 25% of the genes). A large proportion of genes involved in metabolism was up-regulated at 30 degrees C in stationary phase. Conversely, genes up-regulated at 40 degrees C relative to 30 degrees C include those encoding virulence factors such as hemolysins and extracellular secreted proteins with LPXTG motifs. Over-expression of hemolysins was linked to larger zones of hemolysis and enhanced hemolytic activity at 40 degrees C. A key theme identified by our study was that genes involved in purine metabolism and iron acquisition were significantly up-regulated at 40 degrees C. CONCLUSION/SIGNIFICANCE: Growth of GBS in vitro at different temperatures resulted in extensive remodeling of the transcriptome, including genes encoding proven and putative virulence genes. The data provide extensive new leads for molecular pathogenesis research
Group B Streptococcal β-Hemolysin/Cytolysin Directly Impairs Cardiomyocyte Viability and Function
BACKGROUND: Group B Streptococcus (GBS) is a leading cause of neonatal sepsis where myocardial dysfunction is an important contributor to poor outcome. Here we study the effects of the GBS pore-forming beta-hemolysin/cytolysin (Bh/c) exotoxin on cardiomyocyte viability, contractility, and calcium transients. METHODOLOGY/PRINCIPAL FINDINGS: HL-1 cardiomyocytes exposed to intact wild-type (WT) or isogenic Deltabeta h/c mutant GBS, or to cell-free extracts from either strain, were assessed for viability by trypan blue exclusion and for apoptosis by TUNEL staining. Functionality of exposed cardiomyocytes was analyzed by visual quantitation of the rate and extent of contractility. Mitochondrial membrane polarization was measured in TMRE-loaded cells exposed to GBS beta h/c. Effects of GBS beta h/c on calcium transients were studied in fura-2AM-loaded primary rat ventricular cardiomyocytes. Exposure of HL-1 cardiomyocytes to either WT GBS or beta h/c extracts significantly reduced both rate and extent of contractility and later induced necrotic and apoptotic cell death. No effects on cardiomyocyte viability or function were observed after treatment with Deltabeta h/c mutant bacteria or extracts. The beta h/c toxin was associated with complete and rapid loss of detectable calcium transients in primary neonatal rat ventricular cardiomyocytes and induced a loss of mitochondrial membrane polarization. These effects on viability and function were abrogated by the beta h/c inhibitor, dipalmitoyl phosphatidylcholine (DPPC). CONCLUSIONS/SIGNIFICANCE: Our data show a rapid loss of cardiomyocyte viability and function induced by GBS beta h/c, and these deleterious effects are inhibited by DPPC, a normal constituent of human pulmonary surfactant.. These findings have clinical implications for the cardiac dysfunction observed in neonatal GBS infections
Morphology of the bone marrow, spleen and liver during hematopoietic cell mobilization with cyclophosphamide in mice.
Over-the-Counter Monocyclic Non-Steroidal Anti-Inflammatory Drugs in Environment—Sources, Risks, Biodegradation
Recently, the increased use of monocyclic
non-steroidal anti-inflammatory drugs has resulted in
their presence in the environment. This may have
potential negative effects on living organisms. The
biotransformation mechanisms of monocyclic nonsteroidal
anti-inflammatory drugs in the human body
and in other mammals occur by hydroxylation and
conjugation with glycine or glucuronic acid.
Biotransformation/biodegradation of monocyclic
non-steroidal anti-inflammatory drugs in the environment
may be caused by fungal or bacterial microorganisms.
Salicylic acid derivatives are degraded by
catechol or gentisate as intermediates which are
cleaved by dioxygenases. The key intermediate of
the paracetamol degradation pathways is hydroquinone.
Sometimes, after hydrolysis of this drug, 4-
aminophenol is formed, which is a dead-end metabolite.
Ibuprofen is metabolized by hydroxylation or
activation with CoA, resulting in the formation of
isobutylocatechol. The aim of this work is to attempt
to summarize the knowledge about environmental risk
connected with the presence of over-the-counter antiinflammatory
drugs, their sources and the biotransformation
and/or biodegradation pathways of these
drugs
The effect of seminal plasma cadmium and lead levels on semen parameters in male subjects of infertile couples: a prospective cohort study
Different levels of Cd45pos leukocytes in the semen of patients with low testicular volume
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