Aliment Pharmacol Ther 2011; 33: 880–894
Summary
Background From a classical point of view, gastric motility acts to clear the stomach between meals, whereas postprandial motility acts to provide a ...reservoir for food, mixing and grinding the food and to assure a controlled flow of food to the intestines.
Aim To summarise findings that support the role of gastric motility as a central mediator of hunger, satiation and satiety.
Methods A literature review using the search terms ‘satiety’, ‘satiation’ and ‘food intake’ was combined with specific terms corresponding to the sequence of events during and after food intake.
Results During food intake, when gastric emptying of especially solids is limited, gastric distension and gastric accommodation play an important function in the regulation of satiation. After food intake, when the stomach gradually empties, the role of gastric distension in the determination of appetite decreases and the focus will shift to gastric emptying and intestinal exposure of the nutrients. Finally, we have discussed the role of the empty stomach and the migrating motor complex in the regulation of hunger signals.
Conclusions Our findings indicate that gastric motility is a key mediator of hunger, satiation and satiety. More specifically, gastric accommodation and gastric emptying play important roles in the regulation of gastric (dis)tension and intestinal exposure of nutrients and hence control satiation and satiety. Correlations between gastric accommodation, gastric emptying and body weight indicate that gastric motility can also play a role in the long‐term regulation of body weight.
Although insect herbivores and fungal pathogens frequently share the same individual host plant, we lack general insights in how fungal infection affects insect preference and performance. We ...addressed this question in a meta-analysis of 1,113 case studies gathered from 101 primary papers that compared preference or performance of insect herbivores on control vs. fungus challenged plants. Generally, insects preferred, and performed better on, not challenged plants, regardless of experimental conditions. Insect response to fungus infection significantly differed according to fungus lifestyle, insect feeding guild, and the spatial scale of the interaction (local/distant). Insect performance was reduced on plants challenged by biotrophic pathogens or endophytes but not by necrotrophic pathogens. For both chewing and piercing-sucking insects, performance was reduced on challenged plants when interactions occurred locally but not distantly. In plants challenged by biotrophic pathogens, both preference and performance of herbivores were negatively impacted, whereas infection by necrotrophic pathogens reduced herbivore preference more than performance and endophyte infection reduced only herbivore performance. Our study demonstrates that fungi could be important but hitherto overlooked drivers of plant-herbivore interactions, suggesting both direct and plant-mediated effects of fungi on insect’s behavior and development.
Introduction: Selective serotonin reuptake inhibitors (SSRIs) are frequently used in the treatment of irritable bowel syndrome (IBS) although evidence of their efficacy is scarce. Aim: Twenty three ...non-depressed IBS patients were recruited from a tertiary care centre and included in a crossover trial comparing six weeks of treatment with the SSRI citalopram (20 mg for three weeks, 40 mg for three weeks) with placebo. IBS symptom severity was the primary outcome measure, and depression and anxiety scores were also measured. The effect of acute administration of citalopram on colonic sensitivity and on colonic response to feeding was investigated as a putative predictor of symptomatic response to the drug. Results: After three and six weeks of treatment, citalopram significantly improved abdominal pain, bloating, impact of symptoms on daily life, and overall well being compared with placebo. There was only a modest effect on stool pattern. Changes in depression or anxiety scores were not related to symptom improvement. The effect of acute administration of citalopram during a colonic barostat study did not predict clinical outcome. Analysis of the first treatment period as a double blind parallel arm study confirmed the benefit of citalopram over placebo. Conclusions: The SSRI citalopram significantly improves IBS symptoms, including abdominal pain, compared with placebo. The therapeutic effect is independent of effects on anxiety, depression, and colonic sensorimotor function.
Summary
Background
The nonselective 5‐HT4 receptor agonists, cisapride and tegaserod have been associated with cardiovascular adverse events (AEs).
Aim
To perform a systematic review of the safety ...profile, particularly cardiovascular, of 5‐HT4 agonists developed for gastrointestinal disorders, and a nonsystematic summary of their pharmacology and clinical efficacy.
Methods
Articles reporting data on cisapride, clebopride, prucalopride, mosapride, renzapride, tegaserod, TD‐5108 (velusetrag) and ATI‐7505 (naronapride) were identified through a systematic search of the Cochrane Library, Medline, Embase and Toxfile. s from UEGW 2006–2008 and DDW 2008–2010 were searched for these drug names, and pharmaceutical companies approached to provide unpublished data.
Results
Retrieved articles on pharmacokinetics, human pharmacodynamics and clinical data with these 5‐HT4 agonists, are reviewed and summarised nonsystematically. Articles relating to cardiac safety and tolerability of these agents, including any relevant case reports, are reported systematically.
Two nonselective 5‐HT4 agonists had reports of cardiovascular AEs: cisapride (QT prolongation) and tegaserod (ischaemia). Interactions with, respectively, the hERG cardiac potassium channel and 5‐HT1 receptor subtypes have been suggested to account for these effects. No cardiovascular safety concerns were reported for the newer, selective 5‐HT4 agonists prucalopride, velusetrag, naronapride, or for nonselective 5‐HT4 agonists with no hERG or 5‐HT1 affinity (renzapride, clebopride, mosapride).
Conclusions
5‐HT4 agonists for GI disorders differ in chemical structure and selectivity for 5‐HT4 receptors. Selectivity for 5‐HT4 over non‐5‐HT4 receptors may influence the agent's safety and overall risk–benefit profile. Based on available evidence, highly selective 5‐HT4 agonists may offer improved safety to treat patients with impaired GI motility.
Autophagy, an evolutionary conserved process aimed at recycling damaged organelles and protein aggregates in the cell, also modulates proinflammatory cytokine production in peripheral blood ...mononuclear cells. Because adipose tissue inflammation accompanied by elevated levels of proinflammatory cytokines is characteristic for the development of obesity, we hypothesized that modulation of autophagy alters adipose tissue inflammatory gene expression and secretion. We tested our hypothesis using ex vivo and in vivo studies of human and mouse adipose tissue. Levels of the autophagy marker LC3 were elevated in sc adipose tissue of obese vs. lean human subjects and positively correlated to both systemic insulin resistance and morphological characteristics of adipose tissue inflammation. Similarly, autophagic activity levels were increased in adipose tissue of obese and insulin resistant animals as compared with lean mice. Inhibition of autophagy by 3-methylalanine in human and mouse adipose tissue explants led to a significant increase in IL-1β, IL-6, and IL-8 mRNA expression and protein secretion. Noticeably, the enhancement in IL-1β, IL-6, and keratinocyte-derived chemoattractant (KC) by inhibition of autophagy was more robust in the presence of obesity. Similar results were obtained by blocking autophagy using small interfering RNA targeted to ATG7 in human Simpson-Golabi-Behmel syndrome adipocytes. Our results demonstrate that autophagy activity is up-regulated in the adipose tissue of obese individuals and inhibition of autophagy enhances proinflammatory gene expression both in adipocytes and adipose tissue explants. Autophagy may function to dampen inflammatory gene expression and thereby limit excessive inflammation in adipose tissue during obesity.
Summary
Background
When gastro‐oesophageal reflux is causing symptoms or lesions in the oesophagus, this is referred to as gastro‐oesophageal reflux disease (GERD). GERD can manifest itself through ...typical symptoms (heartburn, regurgitation) or may lead to extra‐oesophageal symptoms. Extra‐oesophageal manifestations of GERD gained increasing attention over the last decade, especially respiratory disorders, because of the prevalent co‐occurrence with GERD. The role of GERD in the pathogenesis of respiratory disorders has become a topic of intense discussion.
Aim
To provide an overview of the current knowledge on the role of GERD in asthma and chronic obstructive pulmonary disease (COPD).
Methods
PubMed was searched for relevant articles using the keywords: GERD, asthma, COPD, prevalence, treatment. Case reports were excluded, only English language articles were considered.
Results
Estimates for the prevalence of GERD in asthma range from 30% to 90%, compared to an average of 24% in controls. In COPD patients, the prevalence of GERD ranges from 19% to 78% compared to an average of 18% in controls. These data indicate an increased prevalence of GERD in patients with asthma and COPD, although causality is not established and GERD treatment yielded inconsistent effects. Literature supports GERD as a risk factor for COPD‐exacerbations and a predictor of the ‘frequent‐exacerbator’–phenotype.
Conclusions
Despite the high prevalence of GERD in asthma and COPD, a causal link is lacking. The results of anti‐reflux therapy on pulmonary outcome are inconsistent and contradictory. Future studies will need to identify subgroups of asthmatics and COPD patients that may benefit from anti‐reflux therapy (nocturnal or silent reflux).
Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. Pathways responsible for the activation of IL-1 family cytokines are key in the development of NAFLD but ...underlying mechanisms are not fully understood. Many studies have focused on the inflammasome–caspase-1 pathway and have shown that this pathway is an important inducer of inflammation in NAFLD. However, this pathway is not solely responsible for the activation of proinflammatory cytokines. Also, neutrophil serine proteases (NSPs) are capable of activating cytokines and recent studies reported that these proteases also contribute to NAFLD. These studies provided, for the first time, evidence that this inflammasome-independent pathway is involved in NAFLD. In our opinion, these new insights open up new approaches for therapeutic intervention.
Cytokines are key in the development of NAFLD and NASH but mechanisms responsible for the activation of these cytokines are not fully understood.
The NLRP3–inflammasome pathway is capable of activating cytokines and is a known inducer of inflammation in NAFLD and NASH.
NSPs can also activate cytokines. Studies have now shown that NSPs are also involved in the development of NAFLD and NASH.
The realization that NSPs are involved in NAFLD and NASH in an inflammasome-independent manner provides new insights into how inflammatory pathways contribute to these conditions.
NSPs are inhibited by alpha-1 antitrypsin (AAT), and mice overexpressing AAT are protected against the development of NAFLD. Mice treated with AAT showed reduced hepatic lipid content in NAFLD mice models.
The recent findings that NSPs contribute to NAFLD and NASH may open up perspectives for new therapeutics.
Increasing temperatures and shifting precipitation patterns have major consequences for smallholder farmers, especially in the Global South. Our study examined spatial patterns and climatic drivers ...of farmers' perceptions of climate change, and how these perceptions translated into adaptation actions. We interviewed 56 farmers in southwestern Ethiopia and analyzed ERA5-Land reanalysis climate data from 1971 to 2020. The majority of farmers perceived the recorded temperature increase as well as a decrease and shift in the timing of rainfall. Perceived climate change varied with local climate factors and not with the rate of climate change itself. Farmers' adaptation practices showed associations with local temperature, but not with farmers’ perceptions of climate change. Our findings highlight that even if farmers perceive climate change, perceptions are most common in areas where climate action is already urgent, and perceptions may not translate into adaptation. Thus, targeted and timely information and extension programs are crucial.
Summary
Background
Recent advancements in understanding the roles and functions of glucagon‐like peptide 1 (GLP‐1) and 2 (GLP‐2) have provided a basis for targeting these peptides in therapeutic ...strategies.
Aim
To summarise the preclinical and clinical research supporting the discovery of new therapeutic molecules targeting GLP‐1 and GLP‐2.
Methods
This review is based on a comprehensive PubMed search, representing literature published during the past 30 years related to GLP‐1 and GLP‐2.
Results
Although produced and secreted together primarily from L cells of the intestine in response to ingestion of nutrients, GLP‐1 and GLP‐2 exhibit distinctive biological functions that are governed by the expression of their respective receptors, GLP‐1R and GLP‐2R. Through widespread expression in the pancreas, intestine, nervous tissue, et cetera, GLP‐1Rs facilitates an incretin effect along with effects on appetite and satiety. GLP‐1 analogues resistant to degradation by dipeptidyl peptidase‐IV and inhibitors of dipeptidyl peptidase‐IV have been developed to aid treatment of diabetes and obesity. The GLP‐2R is expressed almost exclusively in the stomach and bowel. The most apparent role for GLP‐2 is its promotion of growth and function of intestinal mucosa, which has been targeted for therapies that promote repair and adaptive growth. These are used as treatments for intestinal failure and related conditions.
Conclusions
Our growing understanding of the biology and function of GLP‐1, GLP‐2 and corresponding receptors has fostered further discovery of fundamental biological function as well as new categories of potent therapeutic medicines.
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