Physiological effects of platyhelminth FMRFamide-related peptides (FaRPs) on the motility of the monogenean Diclidophora merlangi

The actions of known platyhelminth FaRPs on the contractility of whole-worm preparations of the monogenean, Diclidophora merlangi have been examined in vitro for the first time. All of the peptides tested had excitatory effects on the motor activity of the worm. The order of potency for the peptides tested was: YIRFamide > GYIRFamide = RYIRFamide > GNFFRFamide = FLRFamide. However, although YIRFamide was more potent than GYIRFamide, the latter was the most efficacious on each of the motility parameters (tension, contraction amplitude and contraction frequency) examined at concentrations greater than or equal to 0.1 mu M. Serotonin, which stimulates contractility in the worm was used as a positive control. The excitatory activity of turbellarian and cestode neuropeptides on a monogenean indicates at least some structural similarities in the neuropeptide receptors of these classes of flatworm.

Physiological effects of platyhelminth RFamide peptides on muscle-strip preparations of Fasciola hepatica (Trematoda: Digenea)

The effects of each of the known platyhelminth neuropeptides were determined on muscle-strip preparations from the liver fluke, Fasciola hepatica. The activity of synthetic replicates of the C-terminal nonapeptide of neuropeptide F (NPF9, Moniezia expansa), and the FMRFamide-related peptides (FaRPs), GNFFRFamide, RYIRFamide, GYIRFamide and YIRFamide, were examined. Muscle-strip activity was recorded from 1 mm segments of muscle prepared from 28 to 32-day-old worms, using a photo-optic transducer system. None of the peptides (less than or equal to 10 mu M) altered baseline tension significantly; however, each of the peptides increased the amplitude and frequency of muscle contraction. The threshold for activity of each of the peptides examined was, respectively, 1 nM (RYIRFamide), 0.3 mu M (GYIRFamide and YIRFamide), and 10 mu M (GNFFRFamide and NPF9). All of the effects were reversible and repeatable, following wash-out. Muscle-strip integrity was tested following experimentation, using arecoline (10 mu M) and high-K+ bathing medium (90 mM K+).

Pharmacological effects of nematode FMRFamide-related peptides (FaRPs) on muscle contractility of the trematode, Fasciola hepatica

The physiological effects of synthetic replicates of the nematode FaRPs, AF1 (KNEFIRFamide), AF2 (KHEYLRFamide), PF1 (SDPNFLRFamide), PF2 (SADPNFLRFamide), AF8/PF3 (KSAYMRFamide) and PF4 (KPNFIRFamide) were examined on muscle preparations of the liver fluke, Fasciola hepatica. Changes in contractility following the addition of the test compound were recorded using a photo-optic transducer system. Unlike the varied effects these peptides have on nematode somatic musculature, all were found to induce excitatory responses in the muscle activity of F. hepatica. While qualitative effects of the nematode peptides were similar in that they induced increases in both the amplitude and frequency of F. hepatica muscle contractions, they varied considerably in the potency of their excitatory effects. The threshold activity for each peptide was as follows: 10 mu M, PF1 and PF2; 3 mu M, AF1 and PF3; 1 mu M, AF2; and 30 nM, PF4. The results demonstrate, for the first time, the cross-phyla activity of nematode neuropeptides on the neuromuscular activity of a trematode.

Starting slow: the effects of response-switching frequency on patterns of cardiovascular reactivity

Research findings suggest that switching between competing response sets can be resource demanding. The current study focused on concurrent health-relevant physiological effects of task switching by assessing cardiovascular response at varying levels of switch frequency. The participants performed a response-switching task at three different levels of response set switching frequency (low, medium and high) while measurements of blood pressure and heart rate were taken. One group was exposed to response-switching frequency conditions in the order low → medium → high, while the other group was exposed to the same task conditions in the reverse order (i.e. high → medium → low). The results showed that the participants in the low → medium → high switch frequency group recovered faster from initially heightened systolic blood pressure when compared with participants in the high → medium → low group. It is concluded that the results point to a physiological "carry over" effect associated with beginning a task at rapid response switching frequency levels, and suggest the importance of habituation to task demands as a means of offsetting potentially unhealthy levels of reactivity. Implications for modern work environments are discussed.

Effects of the novel (Pro(3))GIP antagonist and exendin(9-39)amide on GIP- and GLP-1-induced cyclic AMP generation, insulin secretion and postprandial insulin release in obese diabetic (ob/ob) mice: evidence that GIP is the major physiological incretin

AIMS/HYPOTHESIS: This study examined the biological effects of the GIP receptor antagonist, (Pro3)GIP and the GLP-1 receptor antagonist, exendin(9-39)amide.

METHODS: Cyclic AMP production was assessed in Chinese hamster lung fibroblasts transfected with human GIP or GLP-1 receptors, respectively. In vitro insulin release studies were assessed in BRIN-BD11 cells while in vivo insulinotropic and glycaemic responses were measured in obese diabetic ( ob/ ob) mice.

RESULTS: In GIP receptor-transfected fibroblasts, (Pro(3))GIP or exendin(9-39)amide inhibited GIP-stimulated cyclic AMP production with maximal inhibition of 70.0+/-3.5% and 73.5+/-3.2% at 10(-6) mol/l, respectively. In GLP-1 receptor-transfected fibroblasts, exendin(9-39)amide inhibited GLP-1-stimulated cyclic AMP production with maximal inhibition of 60+/-0.7% at 10(-6) mol/l, whereas (Pro(3))GIP had no effect. (Pro(3))GIP specifically inhibited GIP-stimulated insulin release (86%; p<0.001) from clonal BRIN-BD11 cells, but had no effect on GLP-1-stimulated insulin release. In contrast, exendin(9-39)amide inhibited both GIP and GLP-1-stimulated insulin release (57% and 44%, respectively; p<0.001). Administration of (Pro(3))GIP, exendin(9-39)amide or a combination of both peptides (25 nmol/kg body weight, i.p.) to fasted (ob/ob) mice decreased the plasma insulin responses by 42%, 54% and 49%, respectively (p<0.01 to p<0.001). The hyperinsulinaemia of non-fasted (ob/ob) mice was decreased by 19%, 27% and 18% (p<0.05 to p<0.01) by injection of (Pro3)GIP, exendin(9-39)amide or combined peptides but accompanying changes of plasma glucose were small.

CONCLUSIONS/INTERPRETATION: These data show that (Pro(3))GIP is a specific GIP receptor antagonist. Furthermore, feeding studies in one commonly used animal model of obesity and diabetes, (ob/ob) mice, suggest that GIP is the major physiological component of the enteroinsular axis, contributing approximately 80% to incretin-induced insulin release.

Effects of trauma on bipolar disorder: the mediational role of interpersonal difficulties and alcohol dependence

Objectives: This study examined: (i) the prevalence of trauma in a bipolar disorder (BD) sample, and (ii) how trauma histories mediated by interpersonal difficulties and alcohol dependence impact on the severity of BD. The prevalence of posttraumatic stress disorder (PTSD) and its relationship to outcomes in BD were also examined.

Methods: Sixty participants were recruited from a geographically well-defined mental health service in Northern Ireland. Self-reported trauma histories, PTSD, interpersonal difficulties and alcohol dependence and were examined in relation to illness severity.

Results: A high prevalence of trauma was found. Trauma predicted the frequency of hospital admissions (R-2 = 0.08), quality of life (R-2 = 0.23) and inter-episode depressive symptoms (R-2 = 0.13). Interpersonal difficulties, but not alcohol dependence, appeared to play an important role in mediating these adverse effects. While only 8% of the sample met criteria for active PTSD, this comorbid disorder was associated with BD severity.

Conclusions: This study indicates that awareness of trauma is important in understanding individual differences in bipolar presentations. The theoretical and clinical implications of evidence that trauma is related to more adverse outcomes in BD are discussed. The finding that interpersonal difficulties mediate the relationship between trauma and BD severity is novel. The need for adjunctive evidence-based treatments targeting interpersonal difficulties is considered.

Investigating the effects of physiological bile acids on GLP-1 secretion and glucose tolerance in normal and GLP-1R(-/-) mice

Physiological secretion of bile acids has previously been linked to the regulation of blood glucose. GLP-1 is an intestinal peptide hormone with important glucose-lowering actions, such as stimulation of insulin secretion and inhibition of glucagon secretion. In this investigation, we assessed the ability of several bile acid compounds to secrete GLP-1 in vitro in STC-1 cells. Bile acids stimulated GLP-1 secretion from 3.3- to 6.2-fold but some were associated with cytolytic effects. Glycocholic and taurocholic acids were selected for in vivo studies in normal and GLP-1R(-/-) mice. Oral glucose tolerance tests revealed that glycocholic acid did not affect glucose excursions. However, taurocholic acid reduced glucose excursions by 40% in normal mice and by 27% in GLP-1R(-/-) mice, and plasma GLP-1 concentrations were significantly elevated 30 min post-gavage. Additional studies used incretin receptor antagonists to probe involvement of GLP-1 and GIP in taurocholic acid-induced glucose lowering. The findings suggest that bile acids partially aid glucose regulation by physiologically enhancing nutrient-induced GLP-1 secretion. However, GLP-1 secretion appears to be only part of the glucose-lowering mechanism and our studies indicate that the other major incretin GIP is not involved.

ALCOHOL-RELATED KNOWLEDGE AND ATTITUDES IN PEOPLE WITH A MILD LEARNING-DISABILITY - THE EFFECTS OF A SENSIBLE DRINKING GROUP

Alcohol-related knowledge and attitudes in people with a mild learning disability, who were either living, or being prepared to live, in relatively independent conditions in the community, were assessed through a structured interview format. Compared with non-learning-disabled teenagers, adults and a hospitalized patient sample, alcohol-related knowledge in the people with a learning disability was found to be significantly poorer, alcohol was reported as having particularly negative effects and susceptibility to social pressure to drink alcohol was greater. A 'sensible drinking' group, taking a social skills and influences approach to alcohol education, was conducted with a subgroup of the individuals with a learning disability. The group format and methods, including in vivo sessions in a public house, are described. Follow-up evaluations suggested some significant positive changes in knowledge, attitudes and sensible drinking skills. It is concluded that this population, which is increasingly living, or being moved into, independent conditions in the community, is at least as vulnerable to social influences on alcohol use and abuse as are young people. As with young people, the usefulness of making available such alcohol-education programmes as described in this study, is discussed.

Physiological stress in the Eurasian badger (Meles meles): Effects of host, disease and environment

A method for monitoring hypothalamic–pituitary–adrenal (HPA) responses of the Eurasian badger (Meles meles) to stressors was validated by measuring cortisol excretion in serum and faeces. Serum and faecal samples were collected under anaesthesia from live-captured, wild badgers and fresh faeces was collected from latrines at 15 social groups in County Down, Northern Ireland. Variation in levels of cortisol in wild badgers was investigated relative to disease status, season, age, sex, body mass, body condition and reproductive status and environmental factors that might influence stress. Faecal cortisol levels were significantly higher in animals testing culture-positive for Mycobacterium bovis. Prolonged elevation of cortisol can suppress immune function, which may have implications for disease transmission. There was a strong seasonal pattern in both serum cortisol, peaking in spring and faecal cortisol, peaking in summer. Cortisol levels were also higher in adults with poor body condition and low body mass. Faecal samples collected from latrines in grassland groups had significantly higher cortisol than those collected from woodland groups, possibly as a result of greater exposure to sources of environmental stress. This study is the first to investigate factors influencing physiological stress in badgers and indicates that serological and faecal excretion are valid indices of the HPA response to a range of stressors.