Small intestinal bacterial overgrowth mimicking acute flare as a pitfall in patients with Crohn's Disease

<p>Abstract</p> <p>Background</p> <p>Small intestinal bacterial overgrowth (SIBO) is characterized by excessive proliferation of colonic bacterial species in the small bowel. Potential causes of SIBO include fistulae, strictures or motility disturbances. Hence, patients with Crohn's Disease (CD) are especially predisposed to develop SIBO. As result, CD patients may experience malabsorption and report symptoms such as weight loss, watery diarrhea, meteorism, flatulence and abdominal pain, mimicking acute flare in these patients.</p> <p>Methods</p> <p>One-hundred-fifty patients with CD reporting increased stool frequency, meteorism and/or abdominal pain were prospectively evaluated for SIBO with the Hydrogen Glucose Breath Test (HGBT).</p> <p>Results</p> <p>Thirty-eight patients (25.3%) were diagnosed with SIBO based on positive findings at HGBT. SIBO patients reported a higher rate of abdominal complaints and exhibited increased stool frequency (5.9 vs. 3.7 bowel movements/day, p = 0.003) and lower body weight (63.6 vs 70.4 kg, p = 0.014). There was no correlation with the Crohn's Disease Activity Index. SIBO was significantly more frequent in patients with partial resection of the colon or multiple intestinal surgeries; there was also a clear trend in patients with ileocecal resection that did not reach statistical significance. SIBO rate was also higher in patients with affection of both the colon and small bowel, while inflammation of the (neo)terminal ileum again showed only tendential association with the development of SIBO.</p> <p>Conclusion</p> <p>SIBO represents a frequently ignored yet clinically relevant complication in CD, often mimicking acute flare. Because symptoms of SIBO are often difficult to differentiate from those caused by the underlying disease, targeted work-up is recommended in patients with corresponding clinical signs and predisposing factors.</p

Physiologically regulated transgenic ABCA1 does not reduce amyloid burden or amyloid‐beta peptide levels in vivo

J Lipid Res. 2007 Apr;48(4):914-23. Epub 2007 Jan 18. Physiologically regulated transgenic ABCA1 does not reduce amyloid burden or amyloid-beta peptide levels in vivo. Hirsch-Reinshagen V, Chan JY, Wilkinson A, Tanaka T, Fan J, Ou G, Maia LF, Singaraja RR, Hayden MR, Wellington CL. Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada. Abstract ABCA1-deficient mice have low levels of poorly lipidated apolipoprotein E (apoE) and exhibit increased amyloid load. To test whether excess ABCA1 protects from amyloid deposition, we crossed APP/PS1 mice to ABCA1 bacterial artificial chromosome (BAC) transgenic mice. Compared with wild-type animals, the ABCA1 BAC led to a 50% increase in cortical ABCA1 protein and a 15% increase in apoE abundance, demonstrating that this BAC supports modest ABCA1 overexpression in brain. However, this was observed only in animals that do not deposit amyloid. Comparison of ABCA1/APP/PS1 mice with APP/PS1 controls revealed no differences in levels of brain ABCA1 protein, amyloid, Abeta, or apoE, despite clear retention of ABCA1 overexpression in the livers of these animals. To further investigate ABCA1 expression in the amyloid-containing brain, we then compared ABCA1 mRNA and protein levels in young and aged cortex and cerebellum of APP/PS1 and ABCA1/APP/PS1 animals. Compared with APP/PS1 controls, aged ABCA1/APP/PS1 mice exhibited increased ABCA1 mRNA, but not protein, selectively in cortex. Additionally, ABCA1 mRNA levels were not increased before amyloid deposition but were induced only in the presence of extensive Abeta and amyloid levels. These data suggest that an induction of ABCA1 expression may be associated with late-stage Alzheimer's neuropathology. PMID: 17235115 [PubMed - indexed for MEDLINE

Shear Viscosity of Clay-like Colloids in Computer Simulations and Experiments

Dense suspensions of small strongly interacting particles are complex systems, which are rarely understood on the microscopic level. We investigate properties of dense suspensions and sediments of small spherical Al_2O_3 particles in a shear cell by means of a combined Molecular Dynamics (MD) and Stochastic Rotation Dynamics (SRD) simulation. We study structuring effects and the dependence of the suspension's viscosity on the shear rate and shear thinning for systems of varying salt concentration and pH value. To show the agreement of our results to experimental data, the relation between bulk pH value and surface charge of spherical colloidal particles is modeled by Debye-Hueckel theory in conjunction with a 2pK charge regulation model.Comment: 15 pages, 8 figure

Ultra late onset group B streptococcal sepsis with acute renal failure in a child with urethral obstruction: a case report

<p>Abstract</p> <p>Introduction</p> <p>Group B streptococci are a well-known cause of early and late onset sepsis. In neonates and older children gram-negative bacteria are mostly found in urinary tract infections and urosepsis. In adults predisposing factors for group B streptococci urinary tract infection may include diabetes mellitus and chronic renal failure.</p> <p>Case presentation</p> <p>We present a rare case of a five-month-old Caucasian boy with ultra late onset urosepsis and acute renal failure caused by group B streptococci serotype V. Excretion urography showed a subvesical obstruction that consequently was surgically corrected after antibiotic treatment of the acute infection.</p> <p>Conclusions</p> <p>Group B streptococci serotype V, urogenitary tract malformations, previous hospitalization and medical interventions may be important risk factors for the development of ultra late onset Group B streptococci sepsis in non-neonates.</p

A screening strategy for the discovery of drugs that reduce C/EBP beta-LIP translation with potential calorie restriction mimetic properties

An important part of the beneficial effects of calorie restriction (CR) on healthspan and lifespan is mediated through regulation of protein synthesis that is under control of the mechanistic target of rapamycin complex 1 (mTORC1). As one of its activities, mTORC1 stimulates translation into the metabolic transcription factor CCAAT/Enhancer Binding Protein beta (C/EBP beta) isoform Liver-specific Inhibitory Protein (LIP). Regulation of LIP expression strictly depends on a translation re-initiation event that requires a conserved cis-regulatory upstream open reading frame (uORF) in the C/EBP beta-mRNA. We showed before that suppression of LIP in mice, reflecting reduced mTORC1-signaling at the C/EBP beta level, results in CR-type of metabolic improvements. Hence, we aim to find possibilities to pharmacologically down-regulate LIP in order to induce CR-mimetic effects. We engineered a luciferasebased cellular reporter system that acts as a surrogate for C/EBP beta-mRNA translation, emulating uORF-dependent C/EBP beta-LIP expression under different translational conditions. By using the reporter system in a high-throughput screening (HTS) strategy we identified drugs that reduce LIP. The drug Adefovir Dipivoxil passed all counter assays and increases fatty acid beta-oxidation in a hepatoma cell line in a LIP-dependent manner. Therefore, these drugs that suppress translation into LIP potentially exhibit CR-mimetic properties

Physics of B_c mesons

In the framework of potential models for heavy quarkonium the mass spectrum for the system ($\bar b c$) is considered. Spin-dependent splittings, taking into account a change of a constant for effective coulomb interaction between the quarks, and widths of radiative transitions between the ($\bar b c$) levels are calculated. In the framework of QCD sum rules, masses of the lightest vector $B_c^*$ and pseudoscalar $B_c$ states are estimated, scaling relation for leptonic constants of heavy quarkonia is derived, and the leptonic constant $f_{B_c}$ is evaluated. The $B_c$ decays are considered in the framework of both the potential models and the QCD sum rules, where the significance of Coulomb-like corrections is shown. The relations, following from the approximate spin symmetry for the heavy quarks in the heavy quarkonium, are analysed for the form factors of the semileptonic weak exclusive decays of $B_c$. The $B_c$ lifetime is evaluated with the account of the corrections to the spectator mechanism of the decay, because of the quark binding into the meson. The total and differential cross sections of the $B_c$ production in different interactions are calculated. The analytic expressions for the fragmentational production cross sections of $B_c$ are derived. The possibility of the practical $B_c$ search in the current and future experiments at electron-positron and hadron colliders is analysed.Comment: 81 page, latex, ihep.sty is required and attached in the end of the file after \end{document}, figures are not availabl

TIA1 Mutations in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Promote Phase Separation and Alter Stress Granule Dynamics.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are age-related neurodegenerative disorders with shared genetic etiologies and overlapping clinical and pathological features. Here we studied a novel ALS/FTD family and identified the P362L mutation in the low-complexity domain (LCD) of T cell-restricted intracellular antigen-1 (TIA1). Subsequent genetic association analyses showed an increased burden of TIA1 LCD mutations in ALS patients compared to controls (p = 8.7 × 1

Open label trial of granulocyte apheresis suggests therapeutic efficacy in chronically active steroid refractory ulcerative colitis

Aim: To study the efficacy, safety, and feasibility of a granulocyte adsorptive type apheresis system for the treatment of patients with chronically active ulcerative colitis despite standard therapy. Methods: An open label multicenter study was carried out in 39 patients with active ulcerative colitis (CAI 6-8) despite continuous use of steroids (a minimum total dose of 400 mg prednisone within the last 4 wk). Patients received a total of five aphereses using a granulocyte adsorptive technique (Adacolumn\uae, Otsuka Pharmaceutical Europe, UK). Assessments at wk 6 and during follow-up until 4 mo comprised clinical (CAI) and endoscopic (EI) activity index, histology, quality of life (IBDQ), and laboratory tests. Results: Thirty-five out of thirty-nine patients were qualified for intent-to-treat analysis. After the apheresis treatment at wk 6, 13/35 (37.1%) patients achieved clinical remission and 10/35 (28.6%) patients had endoscopic remission (CAI<4, EI<4). Quality of life (IBDQ) increased significantly (24 points, P<0.01) at wk 6. Apheresis could be performed in all but one patient. Aphereses were well tolerated, only one patient experienced anemia. Conclusion: In patients with steroid refractory ulcerative colitis, five aphereses with a granulocyte/monocyte depleting filter show potential short-term efficacy. Tolerability and technical feasibility of the procedure are excellent