Characterizing the metabolic effects of the selective inhibition of gut microbial β-glucuronidases in mice

The hydrolysis of xenobiotic glucuronides by gut bacterial glucuronidases reactivates previously detoxified compounds resulting in severe gut toxicity for the host. Selective bacterial β-glucuronidase inhibitors can mitigate this toxicity but their impact on wider host metabolic processes has not been studied. To investigate this the inhibitor 4-(8-(piperazin-1-yl)-1,2,3,4-tetrahydro-[1,2,3]triazino[4′,5′:4,5]thieno[2,3-c]isoquinolin-5-yl)morpholine (UNC10201652, Inh 9) was administered to mice to selectively inhibit a narrow range of bacterial β-glucuronidases in the gut. The metabolomic profiles of the intestinal contents, biofluids, and several tissues involved in the enterohepatic circulation were measured and compared to control animals. No biochemical perturbations were observed in the plasma, liver or gall bladder. In contrast, the metabolite profiles of urine, colon contents, feces and gut wall were altered compared to the controls. Changes were largely restricted to compounds derived from gut microbial metabolism. This work establishes that inhibitors targeted towards bacterial β-glucuronidases modulate the functionality of the intestinal microbiota without adversely impacting the host metabolic system

Simultaneous Determination of Amlodipine and Valsartan

A spectrophotometric method was developed for simultaneous determination of amlodipine (Aml) and valsartan (Val) without previous separation. In this method amlodipine in methanolic solution was determined using zero order UV spectrophotometry by measuring its absorbency at 360.5 nm without any interference from valsartan

Thickness-dependent Electrochromic Properties of Amorphous Tungsten Trioxide Thin Films

Tungsten Trioxide (WO3) thin films were grown by thermal evaporation method to study the effect of film’s thickness on its electrochromic (EC) properties. The WO3 thin films of different thicknesses were grown on Indium Tin Oxide (ITO) coated glass and soda lime (bare) glass substrate held at room temperature. The surface composition of the thin films was investigated using X-ray photoelectron spectroscopy measurement, which showed the oxygen to tungsten atomic composition ratio to be nearly 2.97. The EC properties of the thin films were examined using electrochemical techniques. Cyclic-voltammetery shows the diffusion coefficient (D) of the intercalated H+ ion in the WO3 thin film increases with the film’s thickness. It turns out that the ‘thicker’ film exhibits better coloration efficiency (CE) as compared to the ‘thinner’ film. The coloration time was found to be independent of film thickness; however, the bleaching time increases as the film thickness increases

Thickness-dependent electrochromic properties of amorphous tungsten trioxide thin films

Tungsten Trioxide (WO3) thin films were grown by thermal evaporation method to study the effect of film’s thickness on its electrochromic (EC) properties. The WO3thin films of different thicknesses were grown on Indium Tin Oxide (ITO) coated glass and soda lime (bare) glass substrate held at room temperature. The surface composition of the thin films was investigated using X-ray photoelectron spectroscopy measurement, which showed the oxygen to tungsten atomic composition ratio to be nearly 2.97. The EC properties of the thin films were examined using electrochemical techniques. Cyclic-voltammetery shows the diffusion coefficient (D) of the intercalated H+ ion in the WO3 thin film increases with the film’s thickness. It turns out that the ‘thicker’ film exhibits better coloration efficiency (CE) as compared to the ‘thinner’ film. The coloration time was found to be independent of film thickness; however, the bleaching time increases as the film thickness increases

Thickness-dependent electrochromic properties of amorphous tungsten trioxide thin films

Tungsten Trioxide (WO3) thin films were grown by thermal evaporation method to study the effect of film’s thickness on its electrochromic (EC) properties. The WO3thin films of different thicknesses were grown on Indium Tin Oxide (ITO) coated glass and soda lime (bare) glass substrate held at room temperature. The surface composition of the thin films was investigated using X-ray photoelectron spectroscopy measurement, which showed the oxygen to tungsten atomic composition ratio to be nearly 2.97. The EC properties of the thin films were examined using electrochemical techniques. Cyclic-voltammetery shows the diffusion coefficient (D) of the intercalated H+ ion in the WO3 thin film increases with the film’s thickness. It turns out that the ‘thicker’ film exhibits better coloration efficiency (CE) as compared to the ‘thinner’ film. The coloration time was found to be independent of film thickness; however, the bleaching time increases as the film thickness increases

Metagenomics combined with activity-based proteomics point to gut bacterial enzymes that reactivate mycophenolate

Mycophenolate mofetil (MMF) is an important immunosuppressant prodrug prescribed to prevent organ transplant rejection and to treat autoimmune diseases. MMF usage, however, is limited by severe gastrointestinal toxicity that is observed in approximately 45% of MMF recipients. The active form of the drug, mycophenolic acid (MPA), undergoes extensive enterohepatic recirculation by bacterial beta-glucuronidase (GUS) enzymes, which reactivate MPA from mycophenolate glucuronide (MPAG) within the gastrointestinal tract. GUS enzymes demonstrate distinct substrate preferences based on their structural features, and gut microbial GUS enzymes that reactivate MPA have not been identified. Here, we compare the fecal microbiomes of transplant recipients receiving MMF to healthy individuals using shotgun metagenomic sequencing. We find that neither microbial composition nor the presence of specific structural classes of GUS genes are sufficient to explain the differences in MPA reactivation measured between fecal samples from the two cohorts. We next employed a GUS-specific activity-based chemical probe and targeted metaproteomics to identify and quantify the GUS proteins present in the human fecal samples. The identification of specific GUS enzymes was improved by using the metagenomics data collected from the fecal samples. We found that the presence of GUS enzymes that bind the flavin mononucleotide (FMN) is significantly correlated with efficient MPA reactivation. Furthermore, structural analysis identified motifs unique to these FMN-binding GUS enzymes that provide molecular support for their ability to process this drug glucuronide. These results indicate that FMN-binding GUS enzymes may be responsible for reactivation of MPA and could be a driving force behind MPA-induced GI toxicity.Bio-organic Synthesi

A microscopic approach to the response of 3^{\bf 3}He -4^{\bf 4}He mixtures

Correlated Basis Function perturbation theory is used to evaluate the zero temperature response $S(q,\omega)$ of $^3$He-$^4$He mixtures for inelastic neutron scattering, at momentum transfers $q$ ranging from $1.1$ to $1.7 \AA^{-1}$. We adopt a Jastrow correlated ground state and a basis of correlated particle-hole and phonon states. We insert correlated one particle-one hole and one-phonon states to compute the second order response. The decay of the one-phonon states into two-phonon states is accounted for in boson-boson approximation. The full response is splitted into three partial components $S_{\alpha \beta}(q,\omega)$, each of them showing a particle-hole bump and a one phonon, delta shaped peak, which stays separated from the multiphonon background. The cross term $S_{34}(q,\omega)$ results to be of comparable importance to $S_{33}(q,\omega)$ in the particle-hole sector and to $S_{44}(q,\omega)$ in the phonon one. Once the one-phonon peak has been convoluted with the experimental broadening, the computed scattering function is in semiquantitative agreement with recent experimental measurements.Comment: 26 pages, RevTex 3.0, 8 figures available upon reques

Materiality, health informatics and the limits of knowledge production

© IFIP International Federation for Information Processing 2014 Contemporary societies increasingly rely on complex and sophisticated information systems for a wide variety of tasks and, ultimately, knowledge about the world in which we live. Those systems are central to the kinds of problems our systems and sub-systems face such as health and medical diagnosis, treatment and care. While health information systems represent a continuously expanding field of knowledge production, we suggest that they carry forward significant limitations, particularly in their claims to represent human beings as living creatures and in their capacity to critically reflect on the social, cultural and political origins of many forms of data ‘representation’. In this paper we take these ideas and explore them in relation to the way we see healthcare information systems currently functioning. We offer some examples from our own experience in healthcare settings to illustrate how unexamined ideas about individuals, groups and social categories of people continue to influence health information systems and practices as well as their resulting knowledge production. We suggest some ideas for better understanding how and why this still happens and look to a future where the reflexivity of healthcare administration, the healthcare professions and the information sciences might better engage with these issues. There is no denying the role of health informatics in contemporary healthcare systems but their capacity to represent people in those datascapes has a long way to go if the categories they use to describe and analyse human beings are to produce meaningful knowledge about the social world and not simply to replicate past ideologies of those same categories