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The role of glucocorticoid metabolism in bile acid homeostasis

Opiyo, Monica Naomi; Kenyon, Christopher; Manwani, Kajal; Seckl, Jonathan; Andrew, Ruth; Chapman, Karen (Endocrine Abstracts, 34, 2014)

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Abstract:	Background and aims: Bile acids are conserved through enterohepatic circulation, a glucocorticoid-modulated process. 11β-Hydroxysteroid dehydrogenase type-1 (11β-HSD1) converts cortisone/11-dehydrocortisone to cortisol/corticosterone, thus increasing intracellular glucocorticoid levels. 11β-HSD1 also metabolises 7-oxo-lithocholic acid, a bile acid. 11β-HSD1 is highly expressed in the liver and may alter bile acid transport through regeneration of active glucocorticoids or may directly metabolise bile acids, thus altering profile. We compared bile acid synthesis, release, their enterohepatic circulation and profile in Hsd11b1−/− and isogenic C57Bl/6 control mice. Methods: Adult male, chow-fed mice (eight per group) were fasted for 4 h or fasted for 4 h then re-fed 4 h. Serum, and liver and gall-bladder bile acid concentrations and profiles were measured by spectrophotometry/gas chromatography–mass spectrometry. Results: Fasted Hsd11b1−/− and C57Bl/6 mice had similar volumes of bile (3.2 vs 5.0 l). 7β-Hydroxylated acids (ω-muricholic>β-muricholic>ursodeoxycholic acid>others) predominated in bile of C57Bl/6 mice while 7α-hydroxylated acids (cholic>α-muricholic>chenodeoxycholic acid>others) predominated in Hsd11b1−/− mice; the ratio of 7α:7β acids was >100 greater in Hsd11b1−/−mice. In fasted Hsd11b1− mice, bile acid concentrations were higher in serum (Hsd11b1−/−: 30±9 vs C57Bl/6: 3.8±1.3 nM, P<0.0001) and liver (Hsd11b1−/−: 243±18 vs C57Bl/6: 139±19 nmol/g, P<0.001). Re-feeding caused gall bladder emptying in C57Bl/6 mice (49.6±8% of fasted weight, P<0.0001) and increased serum (62.5±7.6 nM) and liver (497±20 nmol/g) bile acid concentrations, while in Hsd11b1− mice, the gall bladder did not empty (92±7.8% fasted weight) and serum (24±12 nM) and liver (122±21 nmol/g) bile acid concentrations were similar to the fasted state. Conclusion: Bile acid release and the pattern of synthesis is controlled by 11β-HSD1 activity in mice. This may affect digestion and, depending on functional differences of 7α- and 7β- hydroxylated bile acids, may have significant effects on lipid and sterol metabolism and bile acid-mediated transcription.
Description:	Abstract
URI:	http://repository.daystar.ac.ke/xmlui/handle/123456789/3960

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Abstract:	This study focused on community radio in Kenya with an emphasis on the changing nature of community access and participation due to the integration of information and communication technologies (ICTs) in community radio broadcasting. The objectives of the study were to determine how the internet and mobile phones are incorporated into community radio stations, examine the role of ICTs in promoting community participation through the decision making and content production in community radio, and investigate the extent to which ICTs enhance community access to community radio stations. This study was premised upon the domestication theory, the participatory culture model, and Fraser’s (1990) notion of alternative public sphere. It adopted a multiple case study design with the use of in-depth interviews, focus group discussions, document review, and observation for data collection. The findings showed that the radio stations under study, that is, Amani FM, Bus Radio FM, and Kangema RANET FM, demonstrated that they had adapted digital technologies, although the community members did not fully participate in the decision-making process of the stations. The ICTs helped them improve the quality of the radio stations’ programmes, gather news and information, interact with their audiences, and communicate with their sponsors and donors at a greater scale. However, most of the participants still preferred to listen to radio programmes through traditional radio instead of using the internet, social media, or mobile phones. This study recommends that when integrating community radio with ICTs, the needs, perceptions, and expectations of the community radio station and potential challenges that this integration may bring to the community around it should be considered. The access of the community to the ICTs and their level of digital literacy should also be considered.
Description:	Doctor of Philosophy in Communication
URI:	http://repository.daystar.ac.ke/xmlui/handle/123456789/3962

Abstract:	Nano sized powders of TiO2 (titanium dioxide) and Nb2O5 (Niobium (V) oxide) were used to fabricate TiO2/Nb2O5 composites thin films by EPD (electrophoretic deposition) technique. The metal oxide powders, together with magnesium nitrate hexahydrate pellets, were suspended in propan-2-ol inside an EPD cell. The electrodes, placed 1.2 cm apart, were partially immersed in the suspension and a DC potential applied across them. Key EPD process parameters, which include applied DC electric field, deposition time and solid concentration in suspension, were optimized through visual inspection and from UV-Vis-NIR spectrophotometer spectra. The highest (55%) transmittance was obtained for films with deposition time of 90 s, powder concentration of 0.01 g/40 mL, and 35 V DC (direct current) voltage. XRD micrographs confirmed that TiO2 and Nb2O5 particles were presented in the composite film. SEM (scanning electron microscope) micrographs of the composite electrode thin films showed that porous films of high quality with well controlled morphology were deposited by using the EPD technique.
Description:	Journal Article
URI:	http://repository.daystar.ac.ke/xmlui/handle/123456789/3958

Abstract:	This study was prompted by a positional shift on blood rituals amongst central Kenya Christians from the stance of the East African Revival (EAR) members. The study compared the position of contemporary believers, with that of the EARand highlighted the effect theobserved shift might have on the Church. A qualitative strategy with a phenomenological research design and purposive samplingwere applied. In-depth semi-structured interviews, Focus Group Discussions and document review were the research tools. Data was analysed using Thematic Coding Analysis. The EDNA model was used as the theological framework.Findings indicate a significant shift fromscripture as the default, final authority concerningsin and righteousness, to peers and mentors. The oral nature of the EAR’stheological legacy has largely facilitated this shift. Acceptance by the wider society, which values the blood rituals as culture, is valued by the contemporary believer but not by the members of the EAR.
Description:	Journal Article
URI:	http://repository.daystar.ac.ke/xmlui/handle/123456789/3957

Abstract:	For effective interactions to take place in a social network, trust is important. We model trust of agents using the peer to peer reputation ratings in the network that forms a real valued matrix. Singular value decomposition discounts the reputation ratings to estimate the trust levels as trust is the subjective probability of future expectations based on current reputation ratings. Reputation and trust are closely related and singular value decomposition can estimate trust using the real valued matrix of the reputation ratings of the agents in the network. Singular value decomposition is an ideal technique in error elimination when estimating trust from reputation ratings. Reputation estimation of trust is optimal at the discounting of 20 %.
Description:	Journal Article
URI:	http://repository.daystar.ac.ke/xmlui/handle/123456789/3956