Fibrinolytic Activity and Platelet Function in Subjects with Obstructive Sleep Apnoea and a Patent Foramen Ovale: Is There an Option for Prevention of Ischaemic Stroke?

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Moderate hyperuricaemia ameliorated kidney damage in a low-renin model of experimental renal insufficiency

Uric acid has promoted renal fibrosis and inflammation in experimental studies, but some studies have shown nephroprotective effects due to alleviated oxidative stress. We studied the influence of experimental hyperuricaemia in surgically 5/6 nephrectomized rats. Three weeks after subtotal nephrectomy or sham operation, the rats were allocated to control diet or 2.0% oxonic acid (uricase inhibitor) diet for 9 weeks. Then blood, urine and tissue samples were taken, and renal morphology and oxidative stress were examined. Inflammation and fibrosis were evaluated using immunohistochemistry and real-time PCR (RT-PCR). Remnant kidney rats ingesting normal or oxonic acid diet presented with similar to 60% reduction of creatinine clearance and suppressed plasma renin activity. Oxonic acid diet increased plasma uric acid levels by >80 mu mol/L. In remnant kidney rats, moderate hyperuricaemia decreased glomerulosclerosis, tubulointerstitial damage and kidney mast cell count, without influencing the fibrosis marker collagen I messenger RNA (mRNA) content. In both sham-operated and 5/6 nephrectomized rats, the mast cell product 11-epi-prostaglandin-F-2 alpha excretion to the urine and kidney tissue cyclooxygenase-2 (COX-2) levels were decreased. To conclude, hyperuricaemic remnant kidney rats displayed improved kidney morphology and reduced markers of oxidative stress and inflammation. Thus, moderately elevated plasma uric acid had beneficial effects on the kidney in this low-renin model of experimental renal insufficiency.Peer reviewe

Quantifying beetle-mediated effects on gas fluxes from dung pats

Peer reviewe

Quantifying beetle-mediated effects on gas fluxes from dung pats.

Agriculture is one of the largest contributors of the anthropogenic greenhouse gases (GHGs) responsible for global warming. Measurements of gas fluxes from dung pats suggest that dung is a source of GHGs, but whether these emissions are modified by arthropods has not been studied. A closed chamber system was used to measure the fluxes of carbon dioxide (CO2), methane (CH4) and nitrous oxide (N2O) from dung pats with and without dung beetles on a grass sward. The presence of dung beetles significantly affected the fluxes of GHGs from dung pats. Most importantly, fresh dung pats emitted higher amounts of CO2 and lower amounts of CH4 per day in the presence than absence of beetles. Emissions of N2O showed a distinct peak three weeks after the start of the experiment – a pattern detected only in the presence of beetles. When summed over the main grazing season (June–July), total emissions of CH4 proved significantly lower, and total emissions of N2O significantly higher in the presence than absence of beetles. While clearly conditional on the experimental conditions, the patterns observed here reveal a potential impact of dung beetles on gas fluxes realized at a small spatial scale, and thereby suggest that arthropods may have an overall effect on gas fluxes from agriculture. Dissecting the exact mechanisms behind these effects, mapping out the range of conditions under which they occur, and quantifying effect sizes under variable environmental conditions emerge as key priorities for further research

Moderate hyperuricaemia ameliorated kidney damage in a low-renin model of experimental renal insufficiency

Uric acid has promoted renal fibrosis and inflammation in experimental studies, but some studies have shown nephroprotective effects due to alleviated oxidative stress. We studied the influence of experimental hyperuricaemia in surgically 5/6 nephrectomized rats. Three weeks after subtotal nephrectomy or sham operation, the rats were allocated to control diet or 2.0% oxonic acid (uricase inhibitor) diet for 9 weeks. Then blood, urine and tissue samples were taken, and renal morphology and oxidative stress were examined. Inflammation and fibrosis were evaluated using immunohistochemistry and real-time PCR (RT-PCR). Remnant kidney rats ingesting normal or oxonic acid diet presented with similar to 60% reduction of creatinine clearance and suppressed plasma renin activity. Oxonic acid diet increased plasma uric acid levels by >80 mu mol/L. In remnant kidney rats, moderate hyperuricaemia decreased glomerulosclerosis, tubulointerstitial damage and kidney mast cell count, without influencing the fibrosis marker collagen I messenger RNA (mRNA) content. In both sham-operated and 5/6 nephrectomized rats, the mast cell product 11-epi-prostaglandin-F-2 alpha excretion to the urine and kidney tissue cyclooxygenase-2 (COX-2) levels were decreased. To conclude, hyperuricaemic remnant kidney rats displayed improved kidney morphology and reduced markers of oxidative stress and inflammation. Thus, moderately elevated plasma uric acid had beneficial effects on the kidney in this low-renin model of experimental renal insufficiency.Peer reviewe

Fluxes of (a) CO₂ (b) CH₄ (c) N₂O and (d) carbon dioxide equivalents.

<p>Light gray symbols refer to empirical observations, with treatments identified by the same symbol styles as used in Fig. 1. Symbols with 95% confidence limits show least squares means estimated by a GLMM model (for details, see text and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0071454#pone-0071454-t002" target="_blank">Table 2</a>). To reveal overlapping data points, empirical values were slightly offset in the horizontal dimension. As measurements of CH₄ (panel b) and N₂O (panel c) were lost for the first measuring date of 2011, these values are replaced by estimates from a separate experiment conducted in 2012 (see Appendix A for details). For clarity, estimates of 2011 are connected by lines, whereas estimates from 2012 are shown as separate data points (referring to arithmetic means with confidence limits derived from a <i>t</i>-distribution). Note the different scales of the y-axes, and that treatments are identified by the same symbols as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0071454#pone-0071454-g001" target="_blank">Figure 1</a>.</p

Experimental design used in measuring gas fluxes.

<p>(A) Twenty-two mesocosms were placed in an agricultural field, separated by distances of 70 cm. (B) These mesocosms were randomly assigned to three different treatments: 1) dung with dung beetles (open squares; n = 10); 2) dung without dung beetles (filled circles; n = 10), and 3) chambers containing neither dung nor beetles (open triangles; n = 2).</p

Average cumulative fluxes and CO₂ equivalents (g m⁻², ±SD) of greenhouse gases in the different experimental treatments.

a<p>Cumulative fluxes were calculated separately for each chamber as areas under the temporal gas flux curve (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0071454#pone-0071454-g002" target="_blank">Fig. 2</a>; see also Appendix A). For CH₄, N₂O and CO₂ equivalents, measurements from day 1 and 3 were based on a separate experiment conducted in 2012 (see Appendix A), whereas all CO₂ measurements were based on data collected in 2011.</p>b<p>Compound-specific multipliers suggested by the IPCC (2007) were used to weigh together the contribution of individual compounds into the general currency of “CO₂ equivalents”, at a 100-year time horizon. Thus, fluxes of CH₄ were converted to CO₂ equivalents through multiplication by a factor of 25, and fluxes of N₂O through multiplication by a factor of 298. As the net warming impact of carbon first tied by plants, then released from the dung as CO₂ will differ from that of CH₄ or N₂O fluxes from dung (see Discussion), we derive separate subtotals for the cumulative emission of CO₂ equivalents of CH₄, N₂O, and their sum, as well as summing their total (equaling the warming impact of CO₂, CH₄, and N₂O combined).</p>c<p>Row <i>F</i>_B<i>versus F</i>_N shows the results of a compound-specific <i>t</i>-test of treatments <i>F</i>_B (presence of dung beetles) <i>versus F</i>_N (absence of dung beetles). The last row of the table shows the ratio between fluxes in the presence (<i>F</i>_B) <i>versus</i> absence (<i>F</i>_N) of dung beetles as the percentage ((<i>F</i>_B-<i>F</i>_N)/<i>F</i>_N).Variation in degrees of freedom reflects differences between tests based on equal versus unequal variances. (Where not otherwise specified, the test was based on the assumption of equal variances, as supported by a non-significant Levene’s test.).</p>d<p>Test based on unequal variances (cf. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0071454#pone-0071454-g002" target="_blank">Fig. 2c</a>); test of equality of variances, <i>F</i>_9,9 = 3.81 P = 0.03.</p

Generalized linear mixed-effect models of changes in fluxes over time.

a<p>Type 3 <i>F</i>-tests of fixed effects are given.</p>b<p>Mesocosms with 1) dung pats and dung beetles, 2) dung pats and no dung beetles, or 3) neither dung pats nor dung beetles.</p>c<p>Measurement day 1, 6, 10, 15, 20, 30 and 50.</p>d<p>Measurement day 6, 10, 15, 20, 30 and 50.</p

Calcium Carbonate versus Sevelamer Hydrochloride as Phosphate Binders after Long-Term Disease Progression in 5/6 Nephrectomized Rats

Our aim was to compare the effects of calcium carbonate and sevelamer-HCl treatments on calcium-phosphate metabolism and renal function in 5/6 nephrectomized (NX) rats so that long-term disease progression preceded the treatment. After 15-week progression, calcium carbonate (3.0%), sevelamer-HCl (3.0%), or control diets (0.3% calcium) were given for 9 weeks. Subtotal nephrectomy reduced creatinine clearance (−40%), plasma calcidiol (−25%), and calcitriol (−70%) and increased phosphate (+37%), parathyroid hormone (PTH) (11-fold), and fibroblast growth factor-23 (FGF-23) (4-fold). In NX rats, calcium carbonate diet increased plasma (+20%) and urinary calcium (6-fold), reduced plasma phosphate (−50%) and calcidiol (−30%), decreased creatinine clearance (−35%) and FGF 23 (−85%), and suppressed PTH without influencing blood pH. In NX rats, sevelamer-HCl increased urinary calcium (4-fold) and decreased creatinine clearance (−45%), PTH (−75%), blood pH (by 0.20 units), plasma calcidiol (−40%), and calcitriol (−65%). Plasma phosphate and FGF-23 were unchanged. In conclusion, when initiated after long-term progression of experimental renal insufficiency, calcium carbonate diet reduced plasma phosphate and FGF-23 while sevelamer-HCl did not. The former induced hypercalcemia, the latter induced acidosis, while both treatments reduced vitamin D metabolites and deteriorated renal function.Thus, delayed initiation influences the effects of these phosphate binders in remnant kidney rats.Copyright © 2014 Suvi Törmänen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited