Effect of ciliates on nitrification and nitrifying bacteria in Baltic Sea sediments

Nitrification in aquatic sediments is catalyzed by bacteria. While many autecological studies on these bacteria have been published, few have regarded them as part of the benthic microbial food web. Ciliates are important as grazers on bacteria, but also for remineralization of organic matter. We tested the hypothesis that ciliates can affect nitrification. Experiments with Baltic Sea sediments in laboratory flumes, with or without the addition of cultured ciliates, were conducted. We found indication of a higher nitrification potential (ammonium oxidation) in one experiment and increased abundances of nitrifying bacteria in treatments with ciliates. This is likely due to higher nitrogen availability caused by excretion by ciliates and enhanced transport processes in the sediment

Pulmonary delivery of an ultra-fine oxytocin dry powder formulation: potential for treatment of postpartum haemorrhage in developing countries.

Oxytocin is recommended by the World Health Organisation as the most effective uterotonic for the prevention and treatment of postpartum haemorrhage. The requirement for parenteral administration by trained healthcare providers and the need for the drug solution to be maintained under cold-chain storage limit the use of oxytocin in the developing world. In this study, a spray-dried ultrafine formulation of oxytocin was developed with an optimal particle size diameter (1-5 µm) to facilitate aerosolised delivery via the lungs. A powder formulation of oxytocin, using mannitol, glycine and leucine as carriers, was prepared with a volume-based median particle diameter of 1.9 µm. Oxytocin content in the formulation was assayed using high-performance liquid chromatography-mass spectroscopy and was found to be unchanged after spray-drying. Ex vivo contractility studies utilising human and ovine uterine tissue indicated no difference in the bioactivity of oxytocin before and after spray-drying. Uterine electromyographic (EMG) activity in postpartum ewes following pulmonary (in vivo) administration of oxytocin closely mimicked that observed immediately postpartum (0-12 h following normal vaginal delivery of the lamb). In comparison to the intramuscular injection, pulmonary administration of an oxytocin dry powder formulation to postpartum ewes resulted in generally similar EMG responses, however a more rapid onset of uterine EMG activity was observed following pulmonary administration (129 ± 18 s) than intramuscular injection (275 ± 22 s). This is the first study to demonstrate the potential for oxytocin to elicit uterine activity after systemic absorption as an aerosolised powder from the lungs. Aerosolised oxytocin has the potential to provide a stable and easy to administer delivery system for effective prevention and treatment of postpartum haemorrhage in resource-poor settings in the developing world

Dominant-negative effect of the heterozygous C104R TACI mutation in common variable immunodeficiency (CVID)

B cells from patients with common variable immunodeficiency (CVID) who are heterozygous for transmembrane activator and CAML interactor (TACI) mutation C104R, which abolishes ligand binding, fail to produce Igs in response to TACI ligand. It is not known whether this is due to haploinsufficiency or dominant interference. Using in vitro transfection assays, here we demonstrate that C104R and the corresponding murine TACI mutant, C76R, which also does not bind ligand, dominantly interfere with TACI signaling. This effect was dependent on preassociation of the mutants with WT TACI in the absence of ligand. The mutants did not interfere with ligand binding by WT TACI, suggesting that they may act by disrupting ligand-induced receptor rearrangement and signaling. This work demonstrates that TACI preassembles as an oligomeric complex prior to ligand binding and provides a mechanistic insight into how the heterozygous C104R TACI mutation can potentially lead to CVID

<i>Ex vivo</i> assessment of oxytocin induced tracheal smooth muscle contractions.

<p>Effects of applied oxytocin on smooth muscle contractility <i>ex </i><i>vivo</i> using ovine (n=5) tracheal tissue samples. Contraction was normalized as % of the response to acetylcholine (ACh) in PSS. </p

Parameters derived from electromyograph uterine activity in response to oxytocin administration.

<p>Electromyograph (EMG) parameters derived from group EMG profiles outlining; (A) time of onset; (B) duration of initial burst of activity; (C) number of activity bursts per 30 min and; (D) total duration of activity bursts. Data was collected immediately postpartum (PP) and after pulmonary (airway, 200 IU) or IM (10 IU) administration of oxytocin to ewes. Data presented as mean ± SD, n=8.</p

Administration of oxytocin powder formulation to the sheep lung.

<p>Screen images taken (A) prior to; (B) during and (C) 2 min after pulmonary administration of the oxytocin powder formulation above the first bronchial bifurcation.</p

<i>Ex vivo</i> assessment of oxytocin induced uterine smooth muscle contractions.

<p>Effects of applied oxytocin on smooth muscle contractility <i>ex </i><i>vivo</i> using (A) human (n=8) and (B) ovine (n=8) uterine tissue samples. Contraction was normalized as % of the response to high potassium (HiK) in PSS. </p