| 1. |
- Asplund Persson, Anna, 1966-, et al.
(författare)
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Cross-talk between adenosine and the oxatriazole derivative GEA 3175 in platelets
- 2005
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Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 0014-2999 .- 1879-0712. ; 517:3, s. 149-157
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Tidskriftsartikel (refereegranskat)abstract
- We examined the interplay between adenosine and the nitric oxide (NO)-containing oxatriazole derivative GEA 3175 in human platelets. The importance of cyclic guanosine 3′5′-monophosphate (cGMP)-inhibited phosphodiesterases (PDEs) was elucidated by treating the platelets with adenosine combined with either GEA 3175 or the PDE3-inhibitor milrinone. The drug combinations provoked similar cyclic adenosine 3′5′-monophosphate (cAMP) responses. On the contrary, cGMP levels were increased only in GEA 3175-treated platelets. Both drug combinations reduced P-selectin exposure, platelet adhesion and fibrinogen-binding. However, adenosine together with GEA 3175 was more effective in inhibiting platelet aggregation and ATP release. Thrombin-induced rises in cytosolic Ca2+ were suppressed by the two drug combinations. Adenosine administered with GEA 3175 was, however, more effective in reducing Ca2+ influx.In conclusion, the interaction between adenosine and GEA 3175 involves cGMP-mediated inhibition of PDE3. The results also imply that inhibition of Ca2+ influx represent another cGMP-specific mechanism that enhances the effect of adenosine.
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| 2. |
- Liffner, Susanne, et al.
(författare)
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Diagnostics of DNA fragmentation in human spermatozoa: Are sperm chromatin structure analysis and sperm chromatin dispersion tests (SCD-HaloSpermG2 (R)) comparable?
- 2019
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Ingår i: Andrologia. - : WILEY. - 0303-4569 .- 1439-0272. ; 51:8
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Tidskriftsartikel (refereegranskat)abstract
- Men affected with idiopathic infertility often display basic spermiogramme values similar to fertile individuals, questioning the diagnostic impact of the World Health Organization (WHO) thresholds used. This study explored sperm DNA fragmentation in single ejaculates from 14 fertile donors and 42 patients with idiopathic infertility providing semen for assisted reproductive techniques in a university fertility clinic. Each ejaculate was simultaneously studied for sperm DNA fragmentation by the flow cytometer-based sperm chromatin structure analysis (SCSA) and the new light-microscopy-based sperm chromatin dispersion assay (SCD-HaloSpermG2 (R)), before and after sperm selection for in vitro fertilisation with a colloid discontinuous gradient. The WHO semen variables did not differ between groups, but DNA fragmentation after SCSA (DFI) or SCD (SDF) was significantly (p amp;lt; 0.05) higher in patients (DFI: 40.2% +/- 3.0 vs. SDF: 40.3% +/- 1.4) than in fertile donors (DFI: 17.1% +/- 2.1 vs. SDF: 20.9% +/- 2.5). Sperm selection led to lower proportions of DNA-fragmented spermatozoa (DFI: 11.9 +/- 1.7 vs. SCD: 10.0 +/- 0.9, p amp;lt; 0.05). The techniques output correlated highly and significantly (r(2) = 0.82). DNA fragmentation is confirmed as a relevant variable for scrutinising patients with idiopathic infertility, beyond the evidently insufficient WHO semen analyses. Since both techniques yielded similar results, the reduced necessity of complex equipment when running SCD ought to be considered for a clinical setting.
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| 3. |
- Nätt, Daniel, et al.
(författare)
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Human sperm displays rapid responses to diet
- 2019
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Ingår i: PLoS biology. - San Francisco, CA United States : PUBLIC LIBRARY SCIENCE. - 1544-9173 .- 1545-7885. ; 17:12
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Tidskriftsartikel (refereegranskat)abstract
- The global rise in obesity and steady decline in sperm quality are two alarming trends that have emerged during recent decades. In parallel, evidence from model organisms shows that paternal diet can affect offspring metabolic health in a process involving sperm tRNA-derived small RNA (tsRNA). Here, we report that human sperm are acutely sensitive to nutrient flux, both in terms of sperm motility and changes in sperm tsRNA. Over the course of a 2-week diet intervention, in which we first introduced a healthy diet followed by a diet rich in sugar, sperm motility increased and stabilized at high levels. Small RNA-seq on repeatedly sampled sperm from the same individuals revealed that tsRNAs were up-regulated by eating a high-sugar diet for just 1 week. Unsupervised clustering identified two independent pathways for the biogenesis of these tsRNAs: one involving a novel class of fragments with specific cleavage in the T-loop of mature nuclear tRNAs and the other exclusively involving mitochondrial tsRNAs. Mitochondrial involvement was further supported by a similar up-regulation of mitochondrial rRNA-derived small RNA (rsRNA). Notably, the changes in sugar-sensitive tsRNA were positively associated with simultaneous changes in sperm motility and negatively associated with obesity in an independent clinical cohort. This rapid response to a dietary intervention on tsRNA in human sperm is attuned with the paternal intergenerational metabolic responses found in model organisms. More importantly, our findings suggest shared diet-sensitive mechanisms between sperm motility and the biogenesis of tsRNA, which provide novel insights about the interplay between nutrition and male reproductive health.
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| 4. |
- Zalavary, Stefan
(författare)
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Adenosine Regulation of Neutrophil Function
- 1997
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The neutrophil granulocyte is an essential component of the human immune system. When rrricrobes invade the body, the highly motile neutrophils quickly leave the vascular compartment and approach, engulf and kill the intruders by releasing a battery of antimicrobial substances. Adenosine is an endogenous purine nucleoside that is supposed to regulate the inflammatory response, for example, by modulating the activity of neutrophils through occupation of A1 and Az receptors. The aim of the present work was to characterize the effects of adenosine on neutrophil functions, particularly phagocytosis and the production of reactive oxygen species (ROS).Adenosine modulated IgG~mediated phagocytosis in neutrophils in a Ca2+dependent way via stimulatory At and inhibitory Az receptors. The Az receptor~mediated inhibition was associated with an elevation of cAMP, which probably activated protein kinase A (PKA) and thereby interfered with actin dynarrrics and expression of BZ integrins. Production of ROS induced by the chemotactic peptide N~formyl-methionylleucyl~ phenylalanine (fMLP) or IgG~opsonized yeast particles was not affected by occupancy of the At receptor, but was, via a cAMP~dependent mechanism, inhibited by engagement of the A2 receptor. Adenosine also reduced L-selectin-induced production of ROS. The inhibition of ROS production by adenosine was more pronounced during fMLP stimulation than during L~selectin~ and IgG~mediated activation, probably because the latter entailed removal of extracellular adenosine through increased activity of adenosine dearrrinase (ADA).Platelets participate in inflammatory reactions, for instance, by affecting neutrophil actiyity. In the present work, platelets inhibited !MLP~stimulated extracellular generation of ROS by inducing the neutrophils to release adenosine and to form a peripheral actin barrier. In contrast, platelets potentiated IgG~mediated phagocytosis and generation of ROS in neutrophils. This involved engagement of neutrophil Pz receptors by plateletderived ATP and enhanced formation of cortical actin filaments. Expanded ADA activity associated with !gO-stimulation counteracted the inhibitory effects of adenosine accumulated during neutrophil-platelet interaction.In conclusion, this work accentuates the importance of adenosine, both exogenously applied and endogenously formed, as an inflammatory agent modulating the activity of the neutrophil granulocyte.
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