Pharmacokinetics of recombinant human erythropoietin applied subcutaneously to children with chronic renal failure

The single-dose pharmacokinetics of recombinant human erythropoietin (rHuEPO) given SC was investigated in 20 patients aged 7-20 years at different stages of chronic renal failure. In a pilot study we confirmed the lower bioavailability of the drug in 2 children when given SC compared with the IV route (24% and 43%, respectively). Following administration of 4,000 units/m2, rHuEPO SC effective serum erythropoietin concentrations increased from a mean baseline level (+/- SD) of 23 +/- 13 units/l to a mean peak concentration of 265 +/- 123 units/l, which was reached after 14.3 +/- 9.4 h, followed by a slow decline until baseline values were attained at 72 h. Mean residence time was 30 +/- 9 h and mean elimination half-time 14.3 +/- 7 h. The single-dose kinetics of SC rHuEPO in children with different degrees of renal failure are comparable to those in adult patients. Possibly, the higher efficacy of SC rHuEPO in patients with renal anaemia compared with IV rHuEPO is related to its prolonged action

Assessment of total body water in paediatric patients on dialysis

Background Various anthropometric techniques are used to assess total body water in children on dialysis; however, their predictive accuracy and precision has not been validated. Methods We compared total body water measurements obtained by deuterium oxide (D2O) dilution with predictions of total body water from (1) height and weight, (2) skinfold measurements, and (3) bioelectrical impedance analysis, using previously published formulae for healthy children. Measurements were performed in 14 patients on peritoneal and in nine patients on haemodialysis, aged 4-22 years. Results In the total population of dialysed patients, weight was the strongest single predictor of total body water (R2=0.93) followed by the resistance index (RI=height2/impedance; R2=0.85) and height (R2=0.93). A prediction formula based on height and weight predicted total body water with a residual mean square error (RMSE) of 1.97 l (coefficient of variation (CV)=10.0%) and with a systematic overestimation of true total body water by 0.4%. A prediction equation based on skinfold measurements yielded a total body water estimate with an RMSE of 2.15 1 (CV=10.5%) and overpredicted true total body water by an average of 2.2%. Using three published prediction equations incorporating RI, RMSEs of 2.78 1 (CV=14.1%) with a mean under- or overestimation of true total body water by 6.9, 7.1, and 0.8% respectively, were achieved. The prediction of total body water was optimized by linear combinations of RI or the log-transformed sum of four skinfolds (logsum) with weight by the following equations: total body water (1) = 9.97−3.13×logsum +0.59×weight (kg) (1) (R2 = 0.951; RMSE=1.67 1; CV = 8.17%). total body water (1) = 1.99 + 0.144 × RI (Ohm/cm2) + 0.40 × weight (kg) (2) (R2 = 0.949; RMSE = 1.671; CV = 8.53%). The fit of these prediction formulae, which were derived from the total population, did not differ significantly between haemo- and peritoneal dialysis patients or between boys and girls. Conclusions Both skinfold measurements and bioelectrical impedance analysis can be used to improve the height- and weight- based prediction of total body water in children on dialysi

Plant origin and ploidy influence gene expression and life cycle characteristics in an invasive weed

Background: Ecological, evolutionary and physiological studies have thus far provided an incomplete picture of why some plants become invasive; therefore we used genomic resources to complement and advance this field. In order to gain insight into the invasive mechanism of Centaurea stoebe we compared plants of three geo-cytotypes, native Eurasian diploids, native Eurasian tetraploids and introduced North American tetraploids, grown in a common greenhouse environment. We monitored plant performance characteristics and life cycle habits and characterized the expression of genes related to constitutive defense and genome stability using quantitative PCR. Results: Plant origin and ploidy were found to have a significant effect on both life cycle characteristics and gene expression, highlighting the importance of comparing appropriate taxonomic groups in studies of native and introduced plant species. We found that introduced populations of C. stoebe exhibit reduced expression of transcripts related to constitutive defense relative to their native tetraploid counterparts, as might be expected based on ideas of enemy release and rapid evolution. Measurements of several vegetative traits were similar for all geo-cytotypes; however, fecundity of tetraploids was significantly greater than diploids, due in part to their polycarpic nature. A simulation of seed production over time predicts that introduced tetraploids have the highest fecundity of the three geo-cytotypes. Conclusion: Our results suggest that characterizing gene expression in an invasive species using populations from both its native and introduced range can provide insight into the biology of plant invasion that can complement traditional measurements of plant performance. In addition, these results highlight the importance of using appropriate taxonomic units in ecological genomics investigations

Karotten von der Saat bis zum Teller - Einfluss von Sorte, Standort, Jahr, Anbauweise und Lagerung auf den Carotingehalt

Karotten sind ergiebige Quellen an a- und ß-Carotin und weiterer sekundärer Pflanzenstoffe (SPS). Es ist bekannt, dass viele SPS auch für Geschmack, Aroma und Farbe eine Rolle spielen. Der Einfluss von Vorernte- und Nacherntefaktoren auf den Gehalt an SPS gewinnt deshalb zunehmend an Bedeutung. Für die Entwicklung eines Qualitätssicherungskonzepts sind die Kenntnisse über die Auswirkung dieser Faktoren unumgänglich

Bypass of DNA interstrand crosslinks by a Rev1-DNA polymerase ζ complex

DNA polymerase ζ (Pol ζ) and Rev1 are essential for the repair of DNA interstrand crosslink (ICL) damage. We have used yeast DNA polymerases η, ζ and Rev1 to study translesion synthesis (TLS) past a nitrogen mustard-based interstrand crosslink (ICL) with an 8-atom linker between the crosslinked bases. The Rev1-Pol ζ complex was most efficient in complete bypass synthesis, by 2-3 fold, compared to Pol ζ alone or Pol η. Rev1 protein, but not its catalytic activity, was required for efficient TLS. A dCMP residue was faithfully inserted across the ICL-G by Pol η, Pol ζ, and Rev1-Pol ζ. Rev1-Pol ζ, and particularly Pol ζ alone showed a tendency to stall before the ICL, whereas Pol η stalled just after insertion across the ICL. The stalling of Pol η directly past the ICL is attributed to its autoinhibitory activity, caused by elongation of the short ICL-unhooked oligonucleotide (a six-mer in our study) by Pol η providing a barrier to further elongation of the correct primer. No stalling by Rev1-Pol ζ directly past the ICL was observed, suggesting that the proposed function of Pol ζ as an extender DNA polymerase is also required for ICL repair

Sperm competition-induced plasticity in the speed of spermatogenesis

Background: Sperm competition between rival ejaculates over the fertilization of ova typically selects for the production of large numbers of sperm. An obvious way to increase sperm production is to increase testis size, and most empirical work has focussed on this parameter. Adaptive plasticity in sperm production rate could also arise due to variation in the speed with which each spermatozoon is produced, but whether animals can respond to relevant environmental conditions by modulating the kinetics of spermatogenesis in this way has not been experimentally investigated. Results: Here we demonstrate that the simultaneously hermaphroditic flatworm Macrostomum lignano exhibits substantial plasticity in the speed of spermatogenesis, depending on the social context: worms raised under higher levels of sperm competition produce sperm faster. Conclusions: Our findings overturn the prevailing view that the speed of spermatogenesis is a static property of a genotype, and demonstrate the profound impact that social environmental conditions can exert upon a key developmental process. We thus identify, to our knowledge, a novel mechanism through which sperm production rate is maximised under sperm competition

Development of a botanical plant protection product from Larix by-products to protect grapevine from Plasmopara viticola

Extracts from European Larch (Larix decidua) were shown to be efficient to control grapevine downy mildew (Plasmopara viticola) under controlled and field conditions. Larixyl acetate and larixol were identified as the active compounds