The effect of pyloromyotomy on serum and luminal gastrin in infants with hypertrophic pyloric stenosis

Previous studies of the pathogenesis of congenital hypertrophic pyloric stenosis (CHPS) have implicated immunoreactive gastrin, although no consistent relationship has been demonstrated. In this study we have examined the effect which pyloromyotomy has on serum and luminal gastrin concentration after a mechanical and protein stimulus. Seventeen infants were examined preoperatively, and 1 week after pyloromyotomy. On each occasion, samples of serum and gastric contents were collected from fasting infants. Sixty cubic centimeters of water was placed into the stomach and further samples collected 20 min later. The water was then aspirated and replaced by 60 cc of 10% peptone broth and a third set of samples collected after 20 min. All samples from each patient were analyzed for immunoreactive gastrin in the same assay. Pyloromyotomy did not alter fasting serum gastrin (119.3 pg +/- 11.9 preop vs 164.7 +/- 29.9 postop) nor did it alter the gastrin response to water. Pyloromyotomy decreased the incremental serum gastrin response to peptone broth (66.6 +/- 16.9 preop vs 18.9 +/- 11.7 postop). Luminal gastrin concentration was not significantly affected by pyloromyotomy. When the pre- and postoperative serum gastrin increments for water and peptone were plotted against the fasting gastrin levels, an inverse relationship was apparent which was statistically significant by regression analysis. Seen in this way, intragastric water and peptone have a dual effect on serum gastrin; a rise if the fasting serum gastrin concentration is low; a fall or lesser rise if the fasting serum gastrin concentration is high. The data suggest that the direction and magnitude of serum gastrin response to intragastric water or peptone is set by the fasting level, and is independent of pyloromyotomy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/23236/1/0000169.pd

Serotonin and Dopamine Protect from Hypothermia/Rewarming Damage through the CBS/ H2S Pathway

Biogenic amines have been demonstrated to protect cells from apoptotic cell death. Herein we show for the first time that serotonin and dopamine increase H2S production by the endogenous enzyme cystathionine-β-synthase (CBS) and protect cells against hypothermia/rewarming induced reactive oxygen species (ROS) formation and apoptosis. Treatment with both compounds doubled CBS expression through mammalian target of rapamycin (mTOR) and increased H2S production in cultured rat smooth muscle cells. In addition, serotonin and dopamine treatment significantly reduced ROS formation. The beneficial effect of both compounds was minimized by inhibition of their re-uptake and by pharmacological inhibition of CBS or its down-regulation by siRNA. Exogenous administration of H2S and activation of CBS by Prydoxal 5′-phosphate also protected cells from hypothermic damage. Finally, serotonin and dopamine pretreatment of rat lung, kidney, liver and heart prior to 24 h of hypothermia at 3°C followed by 30 min of rewarming at 37°C upregulated the expression of CBS, strongly reduced caspase activity and maintained the physiological pH compared to untreated tissues. Thus, dopamine and serotonin protect cells against hypothermia/rewarming induced damage by increasing H2S production mediated through CBS. Our data identify a novel molecular link between biogenic amines and the H2S pathway, which may profoundly affect our understanding of the biological effects of monoamine neurotransmitters

From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways

The human body hosts an enormous abundance and diversity of microbes, which perform a range of essential and beneficial functions. Our appreciation of the importance of these microbial communities to many aspects of human physiology has grown dramatically in recent years. We know, for example, that animals raised in a germ-free environment exhibit substantially altered immune and metabolic function, while the disruption of commensal microbiota in humans is associated with the development of a growing number of diseases. Evidence is now emerging that, through interactions with the gut-brain axis, the bidirectional communication system between the central nervous system and the gastrointestinal tract, the gut microbiome can also influence neural development, cognition and behaviour, with recent evidence that changes in behaviour alter gut microbiota composition, while modifications of the microbiome can induce depressive-like behaviours. Although an association between enteropathy and certain psychiatric conditions has long been recognized, it now appears that gut microbes represent direct mediators of psychopathology. Here, we examine roles of gut microbiome in shaping brain development and neurological function, and the mechanisms by which it can contribute to mental illness. Further, we discuss how the insight provided by this new and exciting field of research can inform care and provide a basis for the design of novel, microbiota-targeted, therapies.GB Rogers, DJ Keating, RL Young, M-L Wong, J Licinio, and S Wesseling