Rebamipide Does Not Protect Against Naproxen-induced Gastric Damage: A Randomized Double-blind Controlled Trial

Rebamipide is a gastroprotective agent with promising results against gastric damage induced by non-steroidal anti-inflammatory drugs. The present study evaluated if rebamipide protects against naproxen-induced gastric damage in healthy volunteers. Changes in gastric PGE2 tissue concentration were also evaluated. Methods: After a preliminary endoscopy to rule out previous gastric macroscopic damage, twenty-four healthy volunteers of both sexes were divided into 2 groups. One group received sodium naproxen 550 mg b.i.d. plus placebo for 7 days, while the other group received sodium naproxen 550 mg b.i.d. plus rebamipide 100 mg b.i.d. At the end of treatment, a new endoscopy was performed. Gastric macroscopic damage was evaluated by the Cryer score and by the modified Lanza score. The primary outcome measure of the trial was the macroscopic damage observed in each treatment group at the end of treatment. Biopsies were collected at both endoscopies for PGE2 quantification and histopathological analysis (secondary outcomes). Tissue PGE2 was quantified by ELISA. The randomization sequence was generated using 3 blocks of 8 subjects each. Volunteers and endoscopists were blind to whether they were receiving rebamipide or placebo. Results: All recruited volunteers completed the trial. Sodium naproxen induced gastric damage in both groups. At the end of the study, median Cryer score was 4 in both groups (Difference = 0; 95% CI = -1 to 0; p = 0.728). In the placebo group, the mean tissue PGE2 concentration was 1005 +/- 129 pg/mL before treatment and 241 +/- 41 pg/mL after treatment (p < 0.001). In the rebamipide group, the mean tissue PGE2 concentration was 999 +/- 109 pg/mL before treatment, and 168 +/- 13 pg/mL after treatment (p < 0.001). There was no difference in mean tissue PGE2 between the two groups (difference = 5; 95% CI from -334.870 to 345.650; p = 0.975). No significant change was observed at the histopathological evaluation, despite the evident macroscopic damage induced by naproxen. Conclusion: Rebamipide does not protect against naproxen-induced gastric damage in healthy volunteers.16Biolab Industria Farmaceutica Ltd

Effects of Aging and Cyclosporin A on Collagen Turnover in Human Gingiva

BACKGROUND: WE AIMED AT CHARACTERIZING THE AGING GINGIVA ANALYZING: i) collagen content and turnover in human gingival tissues and fibroblasts obtained from healthy young and aging subjects. ii) the effect of cyclosporin A administration in human cultured gingival fibroblasts obtained from aging compared to young subjects. METHODS: Morphological analysis was performed on haematoxylin-eosin and Sirius red stained paraffin-embedded gingival biopsies from young and aging healthy subjects. The expression of the main genes and proteins involved in collagen turnover were determined by real time PCR, dot blot and SDS-zymography on cultured young and aging gingival fibroblasts, and after cyclosporin A administration. RESULTS: Our results suggest that in healthy aged people, gingival connective tissue is characterized by a similar collagen content and turnover. Collagen turnover pathways are similarly affected by cyclosporin A treatment in young and aging gingival fibroblasts. CONCLUSIONS: Cyclosporin A administration affects gingival collagen turnover pathways in young and aging fibroblasts at the same extent, suggesting that during aging cyclosporin A administration is not related to relevant collagen turnover modifications

Behavioral and Endocrine Consequences of Simultaneous Exposure to Two Different Stressors in Rats: Interaction or Independence?

Although behavioral and endocrine consequences of acute exposure to stressors have been extensively studied, little is known about how simultaneous exposure to two different stressors interacts to induce short- and long-term effects. In the present experiment we studied this interaction in adult male rats exposed to cat fur odor (impregnated cloth) or immobilization on boards either separately or simultaneously. We reasoned that exposure to the odor of a potential predator while immobilized, may potentiate its negative consequences as compared to exposure to only one of the stressors. Exposure to cat odor elicited the expected reduction of activity and avoidance of the area where the impregnated cloth was located. The endocrine response (plasma levels of ACTH and corticosterone, as a measure of the hypothalamic-pituitary-adrenal axis, HPA) was markedly greater after immobilization than after cat fur odor and no additive effects were found by simultaneous exposure to both stressors. Cat odor, but not immobilization, increased anxiety-like behavior as evaluated in the elevated plus-maze 7 days after the stressors, with no evidence of enhanced HPA activation. In addition, cat odor exposure resulted in long-lasting (8 days later) fear conditioning to the box containing a clean cloth, which was reflected by hypoactivity, avoidance of the cloth area and enhanced HPA activation. All these effects were similarly observed in rats exposed simultaneously to cat odor and immobilization. In rats only exposed to immobilization, only some weak behavioral signs of fear conditioning were found, but HPA activation in response to the context paired to immobilization was enhanced to the same extent as in cat odor-exposed animals, supporting a certain degree of endocrine conditioning. The present results did not reveal important behavioral interactions between the two stressors when animals experienced both simultaneously, whereas some interactions were found regarding HPA activation. Theoretical implications are discussed

A short-term in situ CO2 enrichment experiment on Heron Island (GBR)

Ocean acidification poses multiple challenges for coral reefs on molecular to ecological scales, yet previous experimental studies of the impact of projected CO2 concentrations have mostly been done in aquarium systems with corals removed from their natural ecosystem and placed under artificial light and seawater conditions. The Coral–Proto Free Ocean Carbon Enrichment System (CP-FOCE) uses a network of sensors to monitor conditions within each flume and maintain experimental pH as an offset from environmental pH using feedback control on the injection of low pH seawater. Carbonate chemistry conditions maintained in the −0.06 and −0.22 pH offset treatments were significantly different than environmental conditions. The results from this short-term experiment suggest that the CP-FOCE is an important new experimental system to study in situ impacts of ocean acidification on coral reef ecosystems

Does Environmental Enrichment Reduce Stress? An Integrated Measure of Corticosterone from Feathers Provides a Novel Perspective

Enrichment is widely used as tool for managing fearfulness, undesirable behaviors, and stress in captive animals, and for studying exploration and personality. Inconsistencies in previous studies of physiological and behavioral responses to enrichment led us to hypothesize that enrichment and its removal are stressful environmental changes to which the hormone corticosterone and fearfulness, activity, and exploration behaviors ought to be sensitive. We conducted two experiments with a captive population of wild-caught Clark's nutcrackers (Nucifraga columbiana) to assess responses to short- (10-d) and long-term (3-mo) enrichment, their removal, and the influence of novelty, within the same animal. Variation in an integrated measure of corticosterone from feathers, combined with video recordings of behaviors, suggests that how individuals perceive enrichment and its removal depends on the duration of exposure. Short- and long-term enrichment elicited different physiological responses, with the former acting as a stressor and birds exhibiting acclimation to the latter. Non-novel enrichment evoked the strongest corticosterone responses of all the treatments, suggesting that the second exposure to the same objects acted as a physiological cue, and that acclimation was overridden by negative past experience. Birds showed weak behavioral responses that were not related to corticosterone. By demonstrating that an integrated measure of glucocorticoid physiology varies significantly with changes to enrichment in the absence of agonistic interactions, our study sheds light on potential mechanisms driving physiological and behavioral responses to environmental change

Behaviourally Mediated Phenotypic Selection in a Disturbed Coral Reef Environment

Natural and anthropogenic disturbances are leading to changes in the nature of many habitats globally, and the magnitude and frequency of these perturbations are predicted to increase under climate change. Globally coral reefs are one of the most vulnerable ecosystems to climate change. Fishes often show relatively rapid declines in abundance when corals become stressed and die, but the processes responsible are largely unknown. This study explored the mechanism by which coral bleaching may influence the levels and selective nature of mortality on a juvenile damselfish, Pomacentrus amboinensis, which associates with hard coral. Recently settled fish had a low propensity to migrate small distances (40 cm) between habitat patches, even when densities were elevated to their natural maximum. Intraspecific interactions and space use differ among three habitats: live hard coral, bleached coral and dead algal-covered coral. Large fish pushed smaller fish further from the shelter of bleached and dead coral thereby exposing smaller fish to higher mortality than experienced on healthy coral. Small recruits suffered higher mortality than large recruits on bleached and dead coral. Mortality was not size selective on live coral. Survival was 3 times as high on live coral as on either bleached or dead coral. Subtle behavioural interactions between fish and their habitats influence the fundamental link between life history stages, the distribution of phenotypic traits in the local population and potentially the evolution of life history strategies

Acclimatization of the crustose coralline alga Porolithon onkodes to variable pCO2

Ocean acidification (OA) has important implications for the persistence of coral reef ecosystems, due to potentially negative effects on biomineralization. Many coral reefs are dynamic with respect to carbonate chemistry, and experience fluctuations in pCO2 that exceed OA projections for the near future. To understand the influence of dynamic pCO2 on an important reef calcifier, we tested the response of the crustose coralline alga Porolithon onkodes to oscillating pCO2. Individuals were exposed to ambient (400 ??atm), high (660 ??atm), or variable pCO2 (oscillating between 400/660 ??atm) treatments for 14 days. To explore the potential for coralline acclimatization, we collected individuals from low and high pCO2 variability sites (upstream and downstream respectively) on a back reef characterized by unidirectional water flow in Moorea, French Polynesia. We quantified the effects of treatment on algal calcification by measuring the change in buoyant weight, and on algal metabolism by conducting sealed incubations to measure rates of photosynthesis and respiration. Net photosynthesis was higher in the ambient treatment than the variable treatment, regardless of habitat origin, and there was no effect on respiration or gross photosynthesis. Exposure to high pCO2 decreased P. onkodes calcification by >70%, regardless of the original habitat. In the variable treatment, corallines from the high variability habitat calcified 42% more than corallines from the low variability habitat. The significance of the original habitat for the coralline calcification response to variable, high pCO2 indicates that individuals existing in dynamic pCO2 habitats may be acclimatized to OA within the scope of in situ variability. These results highlight the importance of accounting for natural pCO2 variability in OA manipulations, and provide insight into the potential for plasticity in habitat and species-specific responses to changing ocean chemistry.Funding was provided by grants from the National Science Foundation (OCE-0417412, OCE-10-26852, OCE-1041270) and gifts from the Gordon and Betty Moore Foundation. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript

Genetic association analyses implicate aberrant regulation of innate and adaptive immunity genes in the pathogenesis of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a genetically complex autoimmune disease characterized by loss of immune tolerance to nuclear and cell surface antigens. Previous genome-wide association studies (GWAS) had modest sample sizes, reducing their scope and reliability. Our study comprised 7,219 cases and 15,991 controls of European ancestry, constituting a new GWAS, a meta-analysis with a published GWAS and a replication study. We have mapped 43 susceptibility loci, including ten new associations. Assisted by dense genome coverage, imputation provided evidence for missense variants underpinning associations in eight genes. Other likely causal genes were established by examining associated alleles for cis-acting eQTL effects in a range of ex vivo immune cells. We found an over-representation (n = 16) of transcription factors among SLE susceptibility genes. This finding supports the view that aberrantly regulated gene expression networks in multiple cell types in both the innate and adaptive immune response contribute to the risk of developing SLE