Cholinergic Responses of Schistosoma mansoni

It is concluded that the use of pharmacological agents can provide opportunities to recognize and define similarities and differences in the mechanisms of transmission of nerve impulses in the parasite and the mammalian host. Such studies contribute to better understanding of comparative physiology and of the mode of action of antiparasitic drugs

The Key Events Dose-Response Framework: A Cross-Disciplinary Mode-of-Action Based Approach to Examining Dose-Response and Thresholds

The ILSI Research Foundation convened a cross-disciplinary working group to examine current approaches for assessing dose-response and identifying safe levels of intake or exposure for four categories of bioactive agents—food allergens, nutrients, pathogenic microorganisms, and environmental chemicals. This effort generated a common analytical framework—the Key Events Dose-Response Framework (KEDRF)—for systematically examining key events that occur between the initial dose of a bioactive agent and the effect of concern. Individual key events are considered with regard to factors that influence the dose-response relationship and factors that underlie variability in that relationship. This approach illuminates the connection between the processes occurring at the level of fundamental biology and the outcomes observed at the individual and population levels. Thus, it promotes an evidence-based approach for using mechanistic data to reduce reliance on default assumptions, to quantify variability, and to better characterize biological thresholds. This paper provides an overview of the KEDRF and introduces a series of four companion papers that illustrate initial application of the approach to a range of bioactive agents

Phosphorylase activity in rat uterus after catecholamine administration

The effects of epinephrine, norepinephrine, and isoproterenol on uterine phosphorylase were studied in intact, anesthetized rats. All three agents were found to increase uterine phosphorylase a activity when administered in large doses by intraperitoneal injection. Total phosphorylase activity was unaffected. The time course for the effects of epinephrine on uterine phosphorylase activity and glycogen content was also studied. Peak phosphorylase activation occurred within 5 min after injection, and the effect had disappeared within 1 hr. Increase in phosphorylase a activity was accompanied by a decrease in uterine glycogen levels, which were still depressed at a time when phosphorylase a activity had returned to normal.Epinephrine was shown to stimulate phosphorylase a activity in the uteri of ovariectomized and estrogen-primed rats as well as in normal intact animals. Ovariectomized animals treated with estradiol had higher resting phosphorylase a activity than had normal untreated animals.The relative ability of several adrenergic blocking agents to prevent catecholamineinduced increases in uterine phosphorylase a activity was investigated, It was suggested that the catecholamines produced their effects on the uterus both directly, via [beta]-adrenergic stimulation, and indirectly, via ischemia and resultant tissue anoxia induced by activation of a-adrenergic receptors in the uterine vasculature.The ability of epinephrine to activate uterine phosphorylase when administered by intravenous infusion was also demonstrated.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/32054/1/0000097.pd

Anxiety and Depression in Adults with Autism Spectrum Disorder: A Systematic Review and Meta-analysis

Adults with autism spectrum disorder (ASD) are thought to be at disproportionate risk of developing mental health comorbidities, with anxiety and depression being considered most prominent amongst these. Yet, no systematic review has been carried out to date to examine rates of both anxiety and depression focusing specifically on adults with ASD. This systematic review and meta-analysis examined the rates of anxiety and depression in adults with ASD and the impact of factors such as assessment methods and presence of comorbid intellectual disability (ID) diagnosis on estimated prevalence rates. Electronic database searches for studies published between January 2000 and September 2017 identified a total of 35 studies, including 30 studies measuring anxiety (n = 26 070; mean age = 30.9, s.d. = 6.2 years) and 29 studies measuring depression (n = 26 117; mean age = 31.1, s.d. = 6.8 years). The pooled estimation of current and lifetime prevalence for adults with ASD were 27% and 42% for any anxiety disorder, and 23% and 37% for depressive disorder. Further analyses revealed that the use of questionnaire measures and the presence of ID may significantly influence estimates of prevalence. The current literature suffers from a high degree of heterogeneity in study method and an overreliance on clinical samples. These results highlight the importance of community-based studies and the identification and inclusion of well-characterized samples to reduce heterogeneity and bias in estimates of prevalence for comorbidity in adults with ASD and other populations with complex psychiatric presentations

Long-Term Cold Acclimation Extends Survival Time at 0°C and Modifies the Metabolomic Profiles of the Larvae of the Fruit Fly Drosophila melanogaster

Drosophila melanogaster is a chill-susceptible insect. Previous studies on this fly focused on acute direct chilling injury during cold shock and showed that lower lethal temperature (LLT, approximately -5°C) exhibits relatively low plasticity and that acclimations, both rapid cold hardening (RCH) and long-term cold acclimation, shift the LLT by only a few degrees at the maximum.We found that long-term cold acclimation considerably improved cold tolerance in fully grown third-instar larvae of D. melanogaster. A comparison of the larvae acclimated at constant 25°C with those acclimated at constant 15°C followed by constant 6°C for 2 d (15°C→6°C) showed that long-term cold acclimation extended the lethal time for 50% of the population (Lt(50)) during exposure to constant 0°C as much as 630-fold (from 0.137 h to 86.658 h). Such marked physiological plasticity in Lt(50) (in contrast to LLT) suggested that chronic indirect chilling injury at 0°C differs from that caused by cold shock. Long-term cold acclimation modified the metabolomic profiles of the larvae. Accumulations of proline (up to 17.7 mM) and trehalose (up to 36.5 mM) were the two most prominent responses. In addition, restructuring of the glycerophospholipid composition of biological membranes was observed. The relative proportion of glycerophosphoethanolamines (especially those with linoleic acid at the sn-2 position) increased at the expense of glycerophosphocholines.Third-instar larvae of D. melanogaster improved their cold tolerance in response to long-term cold acclimation and showed metabolic potential for the accumulation of proline and trehalose and for membrane restructuring