Effect of Information and Telephone-Guided Access to Community Support for People with Chronic Kidney Disease: Randomised Controlled Trial

Background

Implementation of self-management support in traditional primary care settings has proved difficult, encouraging the development of alternative models which actively link to community resources. Chronic kidney disease (CKD) is a common condition usually diagnosed in the presence of other co-morbidities. This trial aimed to determine the effectiveness of an intervention to provide information and telephone-guided access to community support versus usual care for patients with stage 3 CKD.

Methods and Findings

In a pragmatic, two-arm, patient level randomised controlled trial 436 patients with a diagnosis of stage 3 CKD were recruited from 24 general practices in Greater Manchester. Patients were randomised to intervention (215) or usual care (221). Primary outcome measures were health related quality of life (EQ-5D health questionnaire), blood pressure control, and positive and active engagement in life (heiQ) at 6 months. At 6 months, mean health related quality of life was significantly higher for the intervention group (adjusted mean difference = 0.05; 95% CI = 0.01, 0.08) and blood pressure was controlled for a significantly greater proportion of patients in the intervention group (adjusted odds-ratio = 1.85; 95% CI = 1.25, 2.72). Patients did not differ significantly in positive and active engagement in life. The intervention group reported a reduction in costs compared with control.

Conclusions

An intervention to provide tailored information and telephone-guided access to community resources was associated with modest but significant improvements in health related quality of life and better maintenance of blood pressure control for patients with stage 3 CKD compared with usual care. However, further research is required to identify the mechanisms of action of the intervention.

Trial Registration

Controlled-Trials.com ISRCTN45433299     

Virtual Screening as a Strategy for the Identification of Xenobiotics Disrupting Corticosteroid Action

Background

Impaired corticosteroid action caused by genetic and environmental influence, including exposure to hazardous xenobiotics, contributes to the development and progression of metabolic diseases, cardiovascular complications and immune disorders. Novel strategies are thus needed for identifying xenobiotics that interfere with corticosteroid homeostasis. 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2) and mineralocorticoid receptors (MR) are major regulators of corticosteroid action. 11β-HSD2 converts the active glucocorticoid cortisol to the inactive cortisone and protects MR from activation by glucocorticoids. 11β-HSD2 has also an essential role in the placenta to protect the fetus from high maternal cortisol concentrations.

Methods and Principal Findings

We employed a previously constructed 3D-structural library of chemicals with proven and suspected endocrine disrupting effects for virtual screening using a chemical feature-based 11β-HSD pharmacophore. We tested several in silico predicted chemicals in a 11β-HSD2 bioassay. The identified antibiotic lasalocid and the silane-coupling agent {"type":"entrez-nucleotide","attrs":{"text":"AB110873","term_id":"44885399","term_text":"AB110873"}}AB110873 were found to concentration-dependently inhibit 11β-HSD2. Moreover, the silane {"type":"entrez-nucleotide","attrs":{"text":"AB110873","term_id":"44885399","term_text":"AB110873"}}AB110873 was shown to activate MR and stimulate mitochondrial ROS generation and the production of the proinflammatory cytokine interleukin-6 (IL-6). Finally, we constructed a MR pharmacophore, which successfully identified the silane {"type":"entrez-nucleotide","attrs":{"text":"AB110873","term_id":"44885399","term_text":"AB110873"}}AB110873.

Conclusions

Screening of virtual chemical structure libraries can facilitate the identification of xenobiotics inhibiting 11β-HSD2 and/or activating MR. Lasalocid and {"type":"entrez-nucleotide","attrs":{"text":"AB110873","term_id":"44885399","term_text":"AB110873"}}AB110873 belong to new classes of 11β-HSD2 inhibitors. The silane {"type":"entrez-nucleotide","attrs":{"text":"AB110873","term_id":"44885399","term_text":"AB110873"}}AB110873 represents to the best of our knowledge the first industrial chemical shown to activate MR. Furthermore, the MR pharmacophore can now be used for future screening purposes.     

Molecular genetics of Kaposi's sarcoma-associated herpesvirus (human herpesvirus-8) epidemiology and pathogenesis.

Kaposi's sarcoma had been recognized as unique human cancer for a century before it manifested as an AIDS-defining illness with a suspected infectious etiology. The discovery of Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus-8, in 1994 by using representational difference analysis, a subtractive method previously employed for cloning differences in human genomic DNA, was a fitting harbinger for the powerful bioinformatic approaches since employed to understand its pathogenesis in KS. Indeed, the discovery of KSHV was rapidly followed by publication of its complete sequence, which revealed that the virus had coopted a wide armamentarium of human genes; in the short time since then, the functions of many of these viral gene variants in cell growth control, signaling apoptosis, angiogenesis, and immunomodulation have been characterized. This critical literature review explores the pathogenic potential of these genes within the framework of current knowledge of the basic herpesvirology of KSHV, including the relationships between viral genotypic variation and the four clinicoepidemiologic forms of Kaposi's sarcoma, current viral detection methods and their utility, primary infection by KSHV, tissue culture and animal models of latent- and lytic-cycle gene expression and pathogenesis, and viral reactivation from latency. Recent advances in models of de novo endothelial infection, microarray analyses of the host response to infection, receptor identification, and cloning of full-length, infectious KSHV genomic DNA promise to reveal key molecular mechanisms of the candidate pathogeneic genes when expressed in the context of viral infection.     

Interactions of an arbuscular mycorrhizal fungus with free or co-encapsulated cells of Rhizobium trifoli and Yarowia lipolytica inoculated into a soil-plant system

Four times higher nodule number was observed when Glomus deserticola (an arbuscular mycorrhizal fungus) was introduced into a soil-plant system as compared to the control inoculated only with Rhizobium trifoli. This symbiotic parameter was further enhanced by Yarowia lipolytica together with an increase in root mycorrhizal infection of about 14%. Soil inoculation with co-encapsulated R. trifoli and Y. lipolytica provoked a 10-fold increase in root nodulation and led to 55% mycorrhization of the test plant.     

Single-Channel Activities of the Human Epithelial Ca2+ Transport Proteins CaT1 and CaT2

The human epithelial channels, CaT1 and CaT2, were expressed in oocytes, and their single-channel characteristics were compared. In the presence of Na⁺ and K⁺ as charge carriers in the pipette solutions, channel activities were observed only when the the extracellular sides of the patches were exposed to nominally Ca²⁺- and Mg²⁺-free solutions. In patches of both CaT1- and CaT2-expressing oocytes, multiple channel openings were observed, but the current levels were higher in CaT2-expressing oocytes, particularly at more negative voltages. With K⁺ as a charge carrier in patches of CaT1-expressing oocytes, the channel activity was low at −10 to −60 mV, but increased dramatically at more negative potentials. This voltage dependence was observed in the presence of both Na⁺ and K⁺. The channel activity with Na⁺, however, was higher at all potentials. Differences between the voltage dependencies for the two cations were also observed in CaT2-expressing oocytes, but the channel activities were higher than those in CaT1-expressing oocytes, particularly in the presence of Na⁺. We also found that low concentrations of extracellular Mg²⁺ (5–50 μm) elicited a strong inhibitory action on the CaT channels. Activation of the CaT1 and CaT2 channels by hyperpolarization and other factors may promote increased Ca²⁺ entry that participates in stimulation of intestinal absorption and renal reabsorption and/or other Ca²⁺ transport mechanisms in epithelial cells. Received: 8 March 2001/Revised: 24 July 2001     

Biodiesel by-products and P-solubilizing microorganisms

Biodiesel derived from renewable biological sources has in recent years emerged as an alternative fuel for transportation sector. Similarly, glycerol, the main co-product of biodiesel production, has received considerable attention as feedstock for producing various value added products including biofertilizers. The aim of this review is to highlight the value-added utilization of glycerol as a substrate in fermentation processes for P-solubilization by free and immobilized cells and as a formulation agent in preparation of commercial products. In the majority of cases, glycerol demonstrates multiple traits and, therefore some routine techniques for P-solubilization when based on glycerol can be attractive from technical and economic point of view.     

Influence of Cd2+ on growth, chlorophyll content, and water relations in young barley plants

Barley (Hordeum vulgare L., cv. Hemus) plants were grown in nutrient solution with or without 54 μM Cd²⁺ for 12 d. A treatment with Cd²⁺ inhibited the growth of young barley plants. The main factor limiting plant growth was net assimilation rate, due to decreased photosynthetic rate and accelerated dark respiration rate. One of the reasons for the reduced photosynthetic rate was the lower chlorophyll and carotenoid content. Cd²⁺ decreased water potential and transpiration rate, but relative water content in leaves of the treated plants was not significantly changed. This revised version was published online in July 2006 with corrections to the Cover Date.     

Selection of O‐negative induced pluripotent stem cell clones for high‐density red blood cell production in a scalable perfusion bioreactor system

ObjectivesLarge‐scale generation of universal red blood cells (RBCs) from O‐negative (O‐ve) human induced pluripotent stem cells (hiPSCs) holds the potential to alleviate worldwide shortages of blood and provide a safe and secure year‐round supply. Mature RBCs and reticulocytes, the immature counterparts of RBCs generated during erythropoiesis, could also find important applications in research, for example in malaria parasite infection studies. However, one major challenge is the lack of a high‐density culture platform for large‐scale generation of RBCs in vitro.Materials and MethodsWe generated 10 O‐ve hiPSC clones and evaluated their potential for mesoderm formation and erythroid differentiation. We then used a perfusion bioreactor system to perform studies with high‐density cultures of erythroblasts in vitro.ResultsBased on their tri‐lineage (and specifically mesoderm) differentiation potential, we isolated six hiPSC clones capable of producing functional erythroblasts. Using the best performing clone, we demonstrated the small‐scale generation of high‐density cultures of erythroblasts in a perfusion bioreactor system. After process optimization, we were able to achieve a peak cell density of 34.7 million cells/ml with 92.2% viability in the stirred bioreactor. The cells expressed high levels of erythroblast markers, showed oxygen carrying capacity, and were able to undergo enucleation.ConclusionsThis study demonstrated a scalable platform for the production of functional RBCs from hiPSCs. The perfusion culture platform we describe here could pave the way for large volume‐controlled bioreactor culture for the industrial generation of high cell density erythroblasts and RBCs.

Human pluripotent stem cell‐derived red blood cells could help alleviate worldwide blood shortages and provide a secure year‐round supply. However, current generation methods lack the necessary scalability. Here, we present the selection of O‐negative hiPSC clones and demonstrate the small‐scale generation of functional erythroblasts in a high‐density perfusion bioreactor system.     

Localization and partial characterization of a rat ovarian granulose cell protein with a monoclonal antibody

Summry— Hybridoma cell lines were obtained from mouse splenocytes sensitized to granulosa cells collected from rat ovaries after gonadotropin stimulation. A monoclonal antibody (5G5) was obtained which reacted with granulosa cells and showed a positive reaction with serum-free conditioned medium containing granulosa cell secreted proteins. Immoblotting of the conditioned medium and light- and electron-microscopic immunocytochemistry of rat ovary show that mAb 5G5 is directed against a 59-kDa protein which is located on the plasma membrane of granulosa cells. Furthermore, the immunoreactivity of the granulosa cells depends both on the degree of follicle development and on the position of the granulosa cells within the follicles. Strong immunoreactivity was observed in the innermost granulosa cell layers, close to the oocyte and the antral cavity. The results obtained show that mAb 5G5 is a useful marker of a 59-kDa granulosa cell protein which might be of importance for the follicle and the occyte maturation.     

Rock phosphate solubilization by Aspergillus niger grown on sugar-beet waste medium

Solubilization of rock phosphate by Aspergillus niger was studied in solid-state fermentation on sugar-beet waste. This combination was selected after testing three agroindustrial waste materials, namely rice hulls, sugar-beet waste and alperujo. Sugar-beet waste was the best substrate for fungal growth with 69% mineralization, followed by rice hulls and alperujo. The fungus was successfully cultivated on sugar-beet waste supplemented with 3.0 g/l rock phosphate, acidifying the medium and thus decreasing the pH to 3–3.5. Solubilization of insoluble phosphate increased during the first half of the process, reaching a maximum of 292 g phosphate/ml, although a part of it was probably consumed by the mycelium.