Eosinophilic gastroenteritis and graft‐versus‐host disease induced by transmission of Norovirus with fecal microbiota transplant

Fecal microbiota transplantation (FMT) was performed to decolonize gastrointestinal tract from antibiotic‐resistant bacteria before allogeneic hematopoietic cells transplantation (alloHCT). AlloHCT was complicated by norovirus gastroenteritis, acute graft‐versus‐host disease, and eosinophilic pancolitis. Norovirus was identified in samples from FMT material. Symptoms resolved after steroids course and second norovirus‐free FMT from another donor.     

Proton pump activation in stimulated parietal cells is regulated by gastric acid secretory capacity: a human study

Under normal physiological conditions, gastric acid production is controlled by a negative feedback mechanism. Proton pump inhibitors, such as pantoprazole, inhibit gastric acid secretion by irreversibly binding and inactivating luminally active hydrogen potassium ATPase. Recovery of acid production after treatment with a proton pump inhibitor is driven by new pump synthesis, activation of existing cytoplasmic pumps, or reversal of proton pump inhibition. The authors measured the time course of the inhibition and recovery of acid secretion in healthy volunteers following intravenous administration of pantoprazole to determine the rate of proton pump activation under maximally stimulated conditions. Gastric acid production was measured in 27 Helicobacter pylori negative healthy volunteers (mean age = 31 +/- 7 years; 17 men, 10 women) who received single doses of intravenous pantoprazole (20, 40, 80, or 120 mg) in the presence of a continuous intravenous infusion of 1 ug/kg/h of pentagastrin. From the time profile of acid secretion, the authors described the rate of change of acid output using an irreversible pharmacodynamic response model represented by the equation dR/dt = -k x R x Cpanto + Ln2/PPR x (Ro-R) and correlated the parameter values with demographic factors and gastric acid measurements. Mean stimulated acid output secretion was 21.6 +/- 18.4 mEq/h (range: 1.6-90.5) prior to the administration of pantoprazole and remained steady for 25 hours after placebo administration. Intravenous pantoprazole inhibited acid output in a dose-response fashion, with maximal inhibition (99.9%) occurring after an 80 mg dose. Mean proton pump recovery time was 37.1 +/- 21.0 hours (range: 6.7-75), and recovery was independent of the dose of pantoprazole. There was no association noted between proton pump recovery time and gender, age, race, body weight, or pantoprazole dose. However, there was an inverse correlation between acid output during baseline stimulation and recovery of acid secretion. Mean proton pump recovery time in stimulated normal human volunteers was 37.1 +/- 21.0 hours, with a range of 6.7 to 75 hours. The authors hypothesize that there may be a normal homeostatic mechanism that maintains acid secretory capability within a normal range by altering the rate of proton pump activation dependent on the individual's parietal cell mass. Abnormalities of this process may be responsible for the development of acid peptic disease in susceptible individuals.     

NoiseChem: An European Commission research project on the effects of exposure to noise and industrial chemicals on hearing and balance

Exposure to multiple physical and chemical agents is common in occupational environments but workplace hazards and occupational safety criteria for combined exposures is lacking. NoiseChem is an European Commission research project examining the effects of exposure to noise and chemicals on hearing and balance. Partners in Sweden, Finland, France, Denmark, UK and Poland with expert guidance from partners in USA will examine workers and study the mechanisms of action in animals to determine the levels of risk associated with joint exposure to noise and solvents. This paper briefly outlines the project details.     

Molecular and structural consequences of early renal allograft injury

BACKGROUND: Chronic allograft nephropathy is an important cause of graft failure. Many donor and recipient factors contribute to its development. Prospective analysis of these factors has been hindered by the lack of sensitive and specific indicators of renal injury. As a consequence protocol biopsies have been increasingly used in the assessment of renal allograft injury. We performed protocol renal allograft biopsies to prospectively examine the role of important determinants and mediators of chronic allograft nephropathy. METHODS: A total of 51 consecutive cadaveric renal transplant recipients entered a randomized prospective study of tacrolimus (Tac) versus cyclosporine (CsA) microemulsion based immunosuppression. Study patients underwent protocol renal allograft biopsies at the time of engraftment and at 3, 6 and 12 months post-transplantation. Biopsies were analyzed by quantitative polymerase chain reaction (PCR) for mRNA for transforming growth factor-beta (TGF-beta), thrombospondin, and fibronectin. Measurements of renal structural injury were estimated by quantitative assessment of interstitial fibrosis and glomerulosclerosis. Changes in profibrotic growth factors and renal structural injury were related to donor and recipient determinants by stepwise regression analysis. RESULTS: Longitudinal assessment of renal injury demonstrated an early and progressive increase in mRNA for TGF-beta, thrombospondin (TSP) and fibronectin (FBN): TGF-beta baseline, 1.9 +/- 0.2 log copies; TGF-beta 6 months, 2.5 +/- 0.2 log copies, P < 0.05 6 months vs. baseline; TSP baseline, 1.9 +/- 0.2 log copies; TSP 6 months, 2.4 +/- 0.2 log copies, P < 0.05 6 months vs. baseline; FBN baseline, 2.0 +/- 0.2 log copies; FBN 12 months, 2.3 +/- 0.2 log copies, P < 0.05 12 months vs. baseline. This increase in profibrotic growth factors within the allograft was associated with a significant increase in interstitial fibrosis (Vvi) on renal biopsies: Vvi baseline, 13 +/- 1%; Vvi 3 months, 18 +/- 1%; Vvi 6 months, 28 +/- 2%; Vvi 12 months, 34 +/- 2%; P < 0.05 3, 6, and 12 months vs. baseline. Histological analysis demonstrated chronic allograft nephropathy in 4% biopsies at 3 months, 12% at 6 months and in 49% at 12 months. These changes in renal structure were not associated with any change in creatinine clearance (CCr): CCr 3 months, 56 +/- 2 mL/min, CCr 24 months, 56 +/- 2 mL/min; P=NS. Stepwise regression analysis of key donor and recipient determinants of chronic renal injury identified calcineurin inhibitors and acute rejection episodes as important factors involved in the development of chronic renal injury. In particular, the use of cyclosporine compared to tacrolimus was associated with a tenfold increase in TGF-beta mRNA (TGF-beta mRNA at 6 months, CsA vs. Tac, 3 +/- 0.3 vs. 2 +/- 0.3 log copies, P < 0.05), interstitial fibrosis (Vvi at 6 months, CsA vs. Tac, 33 +/- 4% vs. 24 +/- 2%, P < 0.05). Changes in growth factors and renal structure predicted impaired renal function (CCr at 12 months, CsA vs. Tac, 53 +/- 4 mL/min vs. 62 +/- 2 mL/min, P < 0.05). Similarly, acute rejection episodes were associated with an accelerated development of interstitial fibrosis (Vvi at 6 months, acute rejection vs. no rejection, 34 +/- 3% vs. 25 +/- 2%; P < 0.05), but not with changes in TGF-beta, thrombospondin or fibronectin expression. CONCLUSION: Our results suggest that structural injury develops early in the natural history of the renal allograft and is mediated, in part, by the early up-regulation of profibrotic growth factors. We have determined that calcineurin inhibitors, in particular cyclosporine, and acute rejection episodes are key factors in the development of renal structural injury.     

Acute toxicity of 2-butyne-1,4-diol in laboratory animals.

Acute toxicity of 2-butyne-1,4-diol (BYD) was evaluated in laboratory animals. The evaluation involved acute oral and dermal toxicity in rats, dermal and ocular irritation in rabbits and skin sensitization in guinea pigs. The oral LD50 values for BYD were 132 mg kg-1 in male rats and 176 mg kg-1 in female rats. Post-mortem histology showed severe damage in lungs, liver and kidneys. In surviving rats, moderate to severe degenerative changes were observed in the liver but only mild lesions in the kidneys. In acute dermal toxicity studies the test chemical was applied either as a solid substance or as 40% aqueous solution at a dose of 5 g kg-1 for 24 h. Within 48 h of application of the diluted test material, half of the rats died. Liver and kidneys were the primary targets and different stages of degeneration, including necrosis, were observed. No deaths occurred after application of the solid substance. In rabbits, BYD was slightly irritant to skin and eyes. No allergic contact dermatitis was observed in guinea pigs.     

Comparative studies on the properdine level in the blood of two groups of students of moderate and increased muscular activity

Summary A comparison of the properdine level in two groups of students with moderate and increased muscular activity showed a rise of the properdine level by 27 to 30% in the blood of the students with increased muscular activity.

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Zusammenfassung Ein Vergleich des Properdinspiegels von zwei Gruppen Jugendlicher mit geringer und größerer körperlicher Aktivität ergab, daß in dem Blut der Studenten mit stärkerer körperlicher Aktivität um 27 bis 30% mehr Properdin enthalten war.

     

The cerefy brain atlases

The Talairach-Tournoux (TT) atlas is probably the most often used brain atlas. We overview briefly the activities in developments of electronic versions of the TT atlas and focus on our more than 10-yr efforts in its continuous enhancement resulting in three main versions: TT-1997, TT-2000, and TT-2004. The recent TT-2004 version is substantially improved over the digitized print original with a higher structure parcellation, better quality and resolution of individual structures, and improved three-dimensional (3D) spatial consistency. It is also much more suitable for developing atlas-based applications owing to pure color-coding (for automatic structure labeling), contour representation (to avoid scan blocking by the overlaid atlas), and color cross-atlas consistency (for the simultaneous use of multiple atlases). We also provide a procedure for 3D spatial consistency improvement and illustrate its use. Finally, we present some of our latest atlas-assisted applications for fast and automatic interpretation of morphological, stroke, and molecular images, and discuss the future steps in TT atlas enhancement.     

Involvement of capsaicin-sensitive afferent nerves and cholecystokinin 2/gastrin receptors in gastroprotection and adaptation of gastric mucosa to Helicobacter pylori-lipopolysaccharide

Lipopolysaccharide (LPS) is one of the virulence factors in the Helicobacter pylori (Hp)-infected stomach, but it remains unknown whether single and prolonged pretreatment with Hp-LPS can affect the course of gastric damage induced by aspirin (ASA). We compared the effects of Hp-LPS with those induced by LPSs isolated from intestinal Bacteroides fragilis, Yersinia enterocolitica, and Campylobacter jejuni applied for 4 days on acute ASA-induced gastric lesions in rats. The area of ASA-induced gastric lesions, gastric blood flow (GBF), expression of mRNA and protein of leptin and plasma leptin, gastrin, interleukin-1beta, and tumor necrosis factor-alpha levels were examined. Single (once) or repeated (five times) i.p. injections of Hp-LPS (1 mg/kg) or intestinal LPSs failed to produce macroscopic gastric damage and did not affect the GBF when compared with vehicle. Hp-LPS injected repeatedly suppressed the gastric acid secretion, up-regulated leptin mRNA and protein, and increased plasma leptin and gastrin levels. Hp-LPS significantly reduced the ASA-induced gastric damage and the accompanying decline in the GBF, and these effects were significantly attenuated by capsaicin denervation and selective antagonism of cholecystokinin-B (CCK2) receptors by RPR-102681 [N-(metoxy-3 phenyl) N-(N-methyl N-phenyl-carbamylmethyl) carbamoylmethyl]-3 ureido]-3 phenyl]-2 propronique] but not by loxiglumide, an antagonist of CCK1 receptors. We conclude that 1) daily application of Hp-LPS enhances gastric mucosal resistance against ASA damage due to the increase of GBF and the expression and release of leptin and gastrin exerting trophic and gastroprotective effects, and 2) this enhanced resistance to ASA damage in Hp-LPS-adapted stomach is mediated by the sensory afferents and specific CCK2/gastrin receptors.