P2X receptors: epithelial ion channels and regulators of salt and water transport.

When the results from electrophysiological studies of renal epithelial cells are combined with data from in vivo tubule microperfusion experiments and immunohistochemical surveys of the nephron, the accumulated evidence suggests that ATP-gated ion channels, P2X receptors, play a specialized role in the regulation of ion and water movement across the renal tubule and are integral to electrolyte and fluid homeostasis. In this short review, we discuss the concept of P2X receptors as regulators of salt and water salvage pathways, as well as acknowledging their accepted role as ATP-gated ion channels

Effect of base–acid properties of the mixtures of water with methanol on the solution enthalpy of selected cyclic ethers in this mixture at 298.15 K

The enthalpies of solution of cyclic ethers: 1,4- dioxane, 12-crown-4 and 18-crown-6 in the mixture of water and methanol have been measured within the whole mole fraction range at T = 298.15 K. Based on the obtained data, the effect of base–acid properties of water– methanol mixtures on the solution enthalpy of cyclic ethers in these mixtures has been analyzed. The solution enthalpy of cyclic ethers depends on acid properties of water– methanol mixtures in the range of high and medium water contents in the mixture. Based on the analysis performed, it can be assumed that in the mixtures of high methanol contents, cyclic ethe

Quantitative cross-species extrapolation between humans and fish: The case of the anti-depressant fluoxetine

This article has been made available through the Brunel Open Access Publishing Fund.Fish are an important model for the pharmacological and toxicological characterization of human pharmaceuticals in drug discovery, drug safety assessment and environmental toxicology. However, do fish respond to pharmaceuticals as humans do? To address this question, we provide a novel quantitative cross-species extrapolation approach (qCSE) based on the hypothesis that similar plasma concentrations of pharmaceuticals cause comparable target-mediated effects in both humans and fish at similar level of biological organization (Read-Across Hypothesis). To validate this hypothesis, the behavioural effects of the anti-depressant drug fluoxetine on the fish model fathead minnow (Pimephales promelas) were used as test case. Fish were exposed for 28 days to a range of measured water concentrations of fluoxetine (0.1, 1.0, 8.0, 16, 32, 64 μg/L) to produce plasma concentrations below, equal and above the range of Human Therapeutic Plasma Concentrations (HTPCs). Fluoxetine and its metabolite, norfluoxetine, were quantified in the plasma of individual fish and linked to behavioural anxiety-related endpoints. The minimum drug plasma concentrations that elicited anxiolytic responses in fish were above the upper value of the HTPC range, whereas no effects were observed at plasma concentrations below the HTPCs. In vivo metabolism of fluoxetine in humans and fish was similar, and displayed bi-phasic concentration-dependent kinetics driven by the auto-inhibitory dynamics and saturation of the enzymes that convert fluoxetine into norfluoxetine. The sensitivity of fish to fluoxetine was not so dissimilar from that of patients affected by general anxiety disorders. These results represent the first direct evidence of measured internal dose response effect of a pharmaceutical in fish, hence validating the Read-Across hypothesis applied to fluoxetine. Overall, this study demonstrates that the qCSE approach, anchored to internal drug concentrations, is a powerful tool to guide the assessment of the sensitivity of fish to pharmaceuticals, and strengthens the translational power of the cross-species extrapolation

What traits are carried on mobile genetic elements, and why?

Although similar to any other organism, prokaryotes can transfer genes vertically from mother cell to daughter cell, they can also exchange certain genes horizontally. Genes can move within and between genomes at fast rates because of mobile genetic elements (MGEs). Although mobile elements are fundamentally self-interested entities, and thus replicate for their own gain, they frequently carry genes beneficial for their hosts and/or the neighbours of their hosts. Many genes that are carried by mobile elements code for traits that are expressed outside of the cell. Such traits are involved in bacterial sociality, such as the production of public goods, which benefit a cell's neighbours, or the production of bacteriocins, which harm a cell's neighbours. In this study we review the patterns that are emerging in the types of genes carried by mobile elements, and discuss the evolutionary and ecological conditions under which mobile elements evolve to carry their peculiar mix of parasitic, beneficial and cooperative genes

Extracorporeal membrane oxygenator as a bridge to successful surgical repair of bronchopleural fistula following bilateral sequential lung transplantation: a case report and review of literature

<p>Abstract</p> <p>Background</p> <p>Lung transplantation (LTx) is widely accepted as a therapeutic option for end-stage respiratory failure in cystic fibrosis. However, airway complications remain a major cause of morbidity and mortality in these patients, serious airway complications like bronchopleural fistula (BPF) are rare, and their management is very difficult.</p> <p>Case presentation</p> <p>A 47-year-old man with end-stage respiratory failure due to cystic fibrosis underwent bilateral sequential lung transplantation. Severe post-operative bleeding occurred due to dense intrapleural adhesions of the native lungs. He was re-explored and packed leading to satisfactory haemostasis. He developed a bronchopleural fistula on the 14^thpost-operative day. The fistula was successfully repaired using pericardial and intercostal vascular flaps with veno-venous extracorporeal membrane oxygenator (VV-ECMO) support. Subsequently his recovery was uneventful.</p> <p>Conclusion</p> <p>The combination of pedicled intercostal and pericardial flaps provide adequate vascular tissue for sealing a large BPF following LTx. Veno-venous ECMO allows a feasible bridge to recovery.</p

Development of a practice guideline for dietary counselling of children with IgE-mediated food allergy

Purpose The incidence of food allergy is increasing globally and whilst there is consensus that dietitians should be involved in its management, the roles that dietitians should fulfill differ between different guidelines and the description of tasks remains unclear. Currently, no Swiss guideline exists to assist dietitians in counselling children with food allergies. There is a need for recommendations that will guide dietitians through the counselling process. The aim of this project was to create a practice guideline for dietary counselling of children with food allergy. Methods Practice guidelines were developed following the Academy of Nutrition and Dietetics stepwise approach. The process consisted of six steps: (1) Determine the scope oft he guideline. (2) Conduct a systematic review. (3) Draft the guideline recommendations using the Nutrition Care Process (NCP) as a framework. (4) Finalise the guideline during a face-to-face meeting. (5) Conduct internal and external review and revise accordingly. (6) Publish guideline. Results The process resulted in 25 recommendations for dietary counselling. Most recommendations are based on expert opinion only, due to the lack of studies in this field and showed similar levels of consensus between the expert group and external review by allergists. However, there were nine recommendations where the consensus differed. Conclusion This guideline provides a comprehensive guide to dietary counselling for food allergy by dietitians in Switzerland. It will inform best practice and improve patient-centred care and encourage a consistent approach, but it will need to be reviewed and updated as more robust evidence is produced

The Ocular Conjunctiva as a Mucosal Immunization Route: A Profile of the Immune Response to the Model Antigen Tetanus Toxoid

Background: In a quest for a needle-free vaccine administration strategy, we evaluated the ocular conjunctiva as an alternative mucosal immunization route by profiling and comparing the local and systemic immune responses to the subcutaneous or conjunctival administration of tetanus toxoid (TTd), a model antigen. Materials and methods: BALB/c and C57BL/6 mice were immunized either subcutaneously with TTd alone or via the conjunctiva with TTd alone, TTd mixed with 2% glycerol or TTd with merthiolate-inactivated whole-cell B. pertussis (wBP) as adjuvants. Mice were immunized on days 0, 7 and 14 via both routes, and an evaluation of the local and systemic immune responses was performed two weeks after the last immunization. Four weeks after the last immunization, the mice were challenged with a lethal dose (2 x LD50) of tetanus toxin. Results: The conjunctival application of TTd in BALB/c mice induced TTd-specific secretory IgA production and skewed the TTd-specific immune response toward a Th1/Th17 profile, as determined by the stimulation of IFN gamma and IL-17A secretion and/or the concurrent pronounced reduction of IL-4 secretion, irrespective of the adjuvant. In conjunctivaly immunized C57BL/6 mice, only TTd administered with wBP promoted the establishment of a mixed Th1/Th17 TTd-specific immune response, whereas TTd alone or TTd in conjunction with glycerol initiated a dominant Th1 response against TTd. Immunization via the conjunctiva with TTd plus wBP adjuvant resulted in a 33% survival rate of challenged mice compared to a 0% survival rate in non-immunized animals (p lt 0.05). Conclusion: Conjunctival immunization with TTd alone or with various adjuvants induced TTd-specific local and systemic immune responses, predominantly of the Th1 type. The strongest immune responses developed in mice that received TTd together with wBP, which implies that this alternative route might tailor the immune response to fight intracellular bacteria or viruses more effectively

Inhibition of transforming growth factor α (TGF-α)-mediated growth effects in ovarian cancer cell lines by a tyrosine kinase inhibitor ZM 252868

The modulating effects of the epidermal growth factor (EGF) receptor-specific tyrosine kinase inhibitor ZM 252868 on cell growth and signalling have been evaluated in four ovarian carcinoma cell lines PE01, PE04, SKOV-3 and PE01CDDP. Transforming growth factor α (TGF-α)-stimulated growth was completely inhibited by concentrations ≥ 0.3 μM in the PE01 and PE04 cell lines and by ≥ 0.1 μM in SKOV-3 cells. TGF-α inhibition of PE01CDDP growth was reversed by concentrations ≥ 0.1 μM ZM 252868. TGF-α-stimulated tyrosine phosphorylation of both the EGF receptor and c-erbB2 receptor in all four cell lines. The inhibitor ZM 252868, at concentrations ≥ 0.3 μM, completely inhibited TGF-α-stimulated tyrosine phosphorylation of the EGF receptor and reduced phosphorylation of the c-erbB2 protein. EGF-activated EGF receptor tyrosine kinase activity was completely inhibited by 3 μM ZM 252868 in PE01, SKOV-3 and PE01CDDP cells. These data indicate that the EGF receptor-targeted TK inhibitor ZM 252868 can inhibit growth of ovarian carcinoma cells in vitro consistent with inhibition of tyrosine phosphorylation at the EGF receptor. © 1999 Cancer Research Campaig

Blood Magnesium, and the Interaction with Calcium, on the Risk of High-Grade Prostate Cancer

Ionized calcium (Ca) and magnesium (Mg) compete as essential messengers to regulate cell proliferation and inflammation. We hypothesized that inadequate Mg levels, perhaps relative to Ca levels (e.g. a high Ca/Mg ratio) are associated with greater prostate cancer risk.In this biomarker sub-study of the Nashville Men's Health Study (NMHS), we included 494 NMHS participants, consisting of 98 high-grade (Gleason≥7) and 100 low-grade cancer cases, 133 prostate intraepithelial neoplasia (PIN) cases, and 163 controls without cancer or PIN at biopsy. Linear and logistic regression were used to determine associations between blood Ca, Mg, and the Ca/Mg ratio across controls and case groups while adjusting for potential confounding factors.Serum Mg levels were significantly lower, while the Ca/Mg ratio was significantly higher, among high-grade cases vs. controls (p = 0.04, p = 0.01, respectively). Elevated Mg was significantly associated with a lower risk of high-grade prostate cancer (OR = 0.26 (0.09, 0.85)). An elevated Ca/Mg ratio was also associated with an increased risk of high-grade prostate cancer (OR = 2.81 (1.24, 6.36) adjusted for serum Ca and Mg). In contrast, blood Ca levels were not significantly associated with prostate cancer or PIN.Mg, Ca, or Ca/Mg levels were not associated with low-grade cancer, PIN, PSA levels, prostate volume, or BPH treatment.Low blood Mg levels and a high Ca/Mg ratio were significantly associated with high-grade prostate cancer. These findings suggest Mg affects prostate cancer risk perhaps through interacting with Ca