Pairs of cyclic AMP analogs that are specifically synergistic for type I and type II CAMP dependent protein kinases mimic thyrotropin effects on the function, differentiation, expression and mitogenesis of dog thyroid cells

The role of the two different isozymes of the cAMP‐dependent protein kinase is still unclear. We have investigated the potential roles for each isozyme in dog thyroid cells, a model in which the function, expression of differentiation and proliferation are positively regulated by thyrotropin acting through cyclic AMP. The dog thyroid contains both type I and type II cAMP‐dependent protein kinases. These isozymes were selectively activated in vitro by type‐I‐directed and type‐II‐directed analog pairs. In thyroid slices, both type‐I directed and type II‐directed analog pairs synergistically activated thyroid hormone synthesis, as measured by incorporation of 131I into proteins and thyroid hormone secretion as determined by the release of butanol‐extractable 131I. In primary cultures of dog thyroid cells both isozyme‐directed analog pairs synergistically enhanced iodide trapping, a marker of differentiation, and DNA synthesis, as measured by the percentage of cells incorporating [3H]thymidine into their nuclei. However, DNA synthesis was more sensitive to type‐I‐directed pairs. The results demonstrate that both cAMP‐dependent protein kinase isozymes can mediate the action of cAMP on function, differentiation expression and cell proliferation in dog thyroid cells.info:eu-repo/semantics/publishe

Stress And Eating Behaviours In Healthy Adults: A Systematic Review And Meta-Analysis

Stress leads to detrimental health outcomes through direct biological and indirect behavioural changes. Stress can lead to disruption to normal eating behaviours, although the strength of these associations is unknown. This is the first meta-analysis to determine the strength of the stress-eating relationship in healthy adults and to explore the impact of potential moderators. Studies included had a clearly defined measure of stress (i.e., any noxious event or episode in one’s environment with the exclusion of emotional distress) that was linked to non-disordered eating. Key terms were searched in Medline, PsycInfo and Ovid databases (23,104 studies identified). 54 studies (combined N = 119,820) were retained in the meta-analysis. A small, positive effect size was found for the stress-overall food intake relationship (Hedges’ g = 0.114). Stress was associated with increased consumption of unhealthy foods (Hedges’ g = 0.116) but decreased consumption of healthy foods (Hedges’ g = -0.111). Only one significant moderator (restraint on stress-unhealthy eating) was identified. This meta-analysis identified the magnitude of the effect of stress on eating behaviour outcomes. Significant heterogeneity was observed that was not explained by the moderators examined. Further research on moderators of the stress-eating relationship is required and should distinguish effects for healthy versus unhealthy eating

Everolimus with Reduced Calcineurin Inhibitor Exposure in Renal Transplantation

Background Everolimus permits reduced calcineurin inhibitor (CNI) exposure, but the efficacy and safety outcomes of this treatment after kidney transplant require confirmation.Methods In a multicenter noninferiority trial, we randomized 2037 de novo kidney transplant recipients to receive, in combination with induction therapy and corticosteroids, everolimus with reduced-exposure CNI (everolimus arm) or mycophenolic acid (MPA) with standard-exposure CNI (MPA arm). The primary end point was treated biopsy-proven acute rejection or eGFR<50 ml/min per 1.73 m2 at post-transplant month 12 using a 10% noninferiority margin.Results In the intent-to-treat population (everolimus n=1022, MPA n=1015), the primary end point incidence was 48.2% (493) with everolimus and 45.1% (457) with MPA (difference 3.2%; 95% confidence interval, -1.3% to 7.6%). Similar between-treatment differences in incidence were observed in the subgroups of patients who received tacrolimus or cyclosporine. Treated biopsy-proven acute rejection, graft loss, or death at post-transplant month 12 occurred in 14.9% and 12.5% of patients treated with everolimus and MPA, respectively (difference 2.3%; 95% confidence interval, -1.7% to 6.4%). De novo donor-specific antibody incidence at 12 months and antibody-mediated rejection rate did not differ between arms. Cytomegalovirus (3.6% versus 13.3%) and BK virus infections (4.3% versus 8.0%) were less frequent in the everolimus arm than in the MPA arm. Overall, 23.0% and 11.9% of patients treated with everolimus and MPA, respectively, discontinued the study drug because of adverse events.Conclusions In kidney transplant recipients at mild-to-moderate immunologic risk, everolimus was noninferior to MPA for a binary composite end point assessing immunosuppressive efficacy and preservation of graft function