Objective
Fetal fractional limb volume has been proposed as a useful measure for quantifying fetal soft tissue development. The aim of this study was to investigate the growth of fractional arm ...volume (AVol) and fractional thigh volume (TVol) of fetuses with maternal gestational diabetes (GDM) compared with those of fetuses with normal glucose tolerance (NGT). We hypothesised fetal fractional limb volume would be larger in the GDM group than in the NGT group in late gestation.
Design
Exploratory observational study.
Setting
Saitama Municipal Hospital.
Sample
A total of 165 (125 NGT and 40 GDM) singleton Japanese pregnant women.
Methods
AVol and TVol were assessed between 20 and 37 weeks’ gestation as cylindrical limb volumes based on 50% of the fetal humeral or femoral diaphysis length. Women were diagnosed as GDM based on the criteria of the Japan Society of Obstetrics and Gynecology.
Main outcome measures
AVol and TVol were compared between women with NGT and those with GDM at each gestational age period (2‐week intervals from 20 to 37 weeks’ gestation).
Results
Overall, 287 ultrasound scans were performed (NGT group, 205 scans; GDM group, 82 scans). There was no significant difference of AVol between the groups before 32 weeks’ gestation. AVol was significantly larger in the GDM group than in the NGT group after 32 weeks’ gestation (P < 0.05). TVol was not statistically different between the groups across gestation.
Conclusions
Detection of variations in fetal AVol may provide greater insight into understanding the origins of altered fetal body proportion in GDM.
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AVol, but not TVol, is significantly larger in fetuses with GDM than in those with NGT after 32 weeks’ gestation.
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AVol, but not TVol, is significantly larger in fetuses with GDM than in those with NGT after 32 weeks’ gestation.
Background
Short‐chain fatty acids (SCFA) are microbial fermentation products absorbed by the colon. We recently reported that activation of the SCFA receptor termed free fatty acid receptor 3 ...(FFA3), expressed on cholinergic nerves, suppresses nicotinic acetylcholine receptor (nAChR)‐mediated transepithelial anion secretion. This study aimed to clarify how activation of neurally expressed FFA3 affects colonic motor function.
Methods
FFA3‐expressing myenteric neurons were identified by immunostaining; contractions of isolated circular muscle strips obtained from rat proximal colon were measured by isometric transducers. The effect of FFA3 agonists on defecation in vivo was examined in an exogenous serotonin‐induced defecation model.
Key Results
FFA3 immunoreactivity was located in nitrergic and cholinergic neurons in the myenteric plexus. In isolated circular muscle strips without mucosa and submucosa, the addition of nicotine (10 μM) or serotonin transiently relaxed the muscle through nitrergic neurons, whereas high concentrations of nicotine (100 μM) induced large‐amplitude contractions that were mediated by cholinergic neurons. Pretreatment with FFA3 agonists inhibited nicotine‐ or serotonin‐induced motility changes but had no effect on bethanechol‐induced direct muscle contractions. The Gi/o inhibitor pertussis toxin reversed the inhibitory effect of an FFA3 agonist AR420626 on nicotine‐evoked contractions, suggesting that FFA3 activation suppresses nAChR‐mediated neural activity in myenteric neurons, consistent with an FFA3‐mediated antisecretory effect. In conscious rats, exogenous serotonin increased the volume of fecal output, compared with the vehicle‐ or AR420626‐treated groups. Pretreatment with AR420626 significantly suppressed serotonin‐induced fecal output.
Conclusion and Inferences
FFA3 is a promising target for the treatment of neurogenic diarrheal disorders by suppressing nAChR‐mediated neural pathways.
Short‐chain fatty acids produced by the gut microbiota contribute to the colonic motility regulation in health and disease. We identified the expression of a short‐chain fatty acid receptor, free fatty acid receptor 3 (FFA3), in inhibitory and excitatory myenteric neurons. The activation of FFA3 inhibited nicotine‐ or serotonin‐induced circular muscle activities ex vivo, and prevented serotonin‐induced defecation in vivo.
Objective
To investigate the association between mid‐trimester residual cervical length (CL) and the risk of preterm birth in pregnancies after abdominal radical trachelectomy (RT).
Design
...Retrospective cohort study.
Setting
University hospital.
Population
A total of 33 deliveries after 22 weeks’ gestation in 30 women who underwent abdominal RT including prophylactic cervical cerclage and perinatal care between January 2002 and May 2016.
Methods
The association between mid‐trimester residual CL (the distance between the cerclage and the external cervical os) and gestational age at delivery was investigated. Receiver–operating characteristics (ROC) curve analysis was performed to estimate the optimal cut‐off values of the mid‐trimester residual CL for the prediction of preterm birth.
Main outcome measures
Preterm birth before 34 weeks’ gestation.
Results
Mid‐trimester residual CL showed a significant correlation with gestational age at delivery (r = 0.36, P < 0.05). There was a significant difference in residual CL between women who did and those who did not give birth before 34 weeks (P < 0.05). Mid‐trimester residual CL < 13 mm was a good predictor of birth before 34 weeks, with a sensitivity of 67%, specificity of 75%, positive predictive value of 55% and negative predictive value of 86% (area under ROC curve, 0.75).
Conclusions
Mid‐trimester residual CL is significantly correlated with gestational age at delivery. Residual CL assessment could be used to reassure physicians and women that there is only a small chance of preterm birth in pregnancies after abdominal RT.
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Mid‐trimester residual cervical length is a good predictor of preterm birth after radical trachelectomy.
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Mid‐trimester residual cervical length is a good predictor of preterm birth after radical trachelectomy.
The field of gut nutrient chemosensing is evolving rapidly. Recent advances have uncovered the mechanism by which specific nutrient components evoke multiple metabolic responses. Deorphanization of G ...protein-coupled receptors (GPCRs) in the gut has helped identify previously unliganded receptors and their cognate ligands. In this review, we discuss nutrient receptors, their ligand preferences, and the evoked neurohormonal responses. Family A GPCRs includes receptor GPR93, which senses protein and proteolytic degradation products, and free fatty acid-sensing receptors. Short-chain free fatty acids are ligands for FFA2, previously GPR43, and FFA3, previously GPR41. FFA1, previously GPR40, is activated by long-chain fatty acids with GPR120 activated by medium- and long-chain fatty acids. The GPR119 agonist ethanolamide oleoylethanolamide (OEA) and bile acid GPR131 agonists have also been identified. Family C receptors ligand preferences include L-amino acids, carbohydrate, and tastants. The metabotropic glutamate receptor (mGluR), calcium-sensing receptor (CaR), and GPCR family C, group 6, subtype A receptor (GPRC6A) mediate L-amino acid-sensing. Taste receptors have a proposed role in intestinal chemosensing; sweet, bitter, and umami evoke responses in the gut via GPCRs. The mechanism of carbohydrate-sensing remains controversial: the heterodimeric taste receptor T1R2/T1R3 and sodium glucose cotransporter 1 (SGLT-1) expressed in L cells are the two leading candidates. Identification of specific nutrient receptors and their respective ligands can provide novel therapeutic targets for the treatment of diabetes, acid reflux, foregut mucosal injury, and obesity.
Heat stress is of major concern for poultry, especially in the hot regions of the world because of the resulting poor growth performance, immunosuppression, and high mortality. To assess superoxide ...(oxygen free radical) production in mitochondria isolated from skeletal muscle of chickens (n = 4 to 8) exposed to acute heat stress, electron spin resonance (ESR) spectroscopy using 5,5-dimethyl-1-pyrroline N-oxide (DMPO) as a spin trap agent and lucigenin-derived chemiluminescence (LDCL) method were applied. ESR spectra of suspensions containing mitochondria from control and acute heat-treated meat-type chickens showed similar hyperfine coupling constants (aN = 1.44 mT, aHbeta = 0.12 mT, and aHbeta = 0.11 mT) to those of DMPO-oxygen free radical adducts observed in a hypoxanthine-xanthine oxidase system. Heat exposure resulted in enhancement of the DMPO-oxygen free radical signal. The results using LDCL showed significantly enhanced superoxide production in heat stress-treated skeletal muscle mitochondria of meat-type chickens, whereas no such increase was observed in laying chickens. The enhancement of superoxide production in the former case was associated with heat-induced increments in rectal and muscle temperatures, leading to significant body weight loss. In contrast, the latter case showed no increase in temperatures, although there was a slight decrease in body weight gain. Percentage increases of superoxide production in the presence of carboxyatractylate, a specific inhibitor of adenine nucleotide translocator (ANT), were the same for skeletal muscle mitochondria from meat- and laying-type chickens from the control or heat stress-treated group. This finding suggests the irrelevance of ANT in the regulation of reactive oxygen species flux under heat stress conditions. The study provides the first evidence of superoxide anion production in the skeletal muscle mitochondria of meat-type chickens in response to acute heat stress.
Background and Purpose
The bioactive monoamine 5‐HT, implicated in the pathogenesis of functional gastrointestinal disorders, is abundantly synthesized and stored in rat proximal colonic mucosa and ...released to the gut lumen and subepithelial space. Despite much data regarding its expression and function, the effects of luminal 5‐HT on colonic anion secretion have not been fully investigated.
Experimental Approach
We measured short‐circuit current (Isc) as an indicator of ion transport in mucosa‐submucosa or mucosa‐only preparations of rat proximal colon. Total CO2 output was measured in vitro and in vivo. Immunohistochemistry was performed to investigate the localization of 5‐HT4, NOS1 and NOS2.
Key Results
Luminal 5‐HT gradually increased the amplitude and sustained the elevation of Isc. Luminal 5‐HT‐evoked ΔIsc was acetazolamide sensitive and HCO3− dependent, consistent with cytosolic carbonic anhydrase‐dependent electrogenic HCO3− secretion, while not affected by tetrodotoxin (TTX), atropine or indomethacin. Pretreatment with the selective 5‐HT4 antagonist GR113808, but not antagonists for 5‐HT3, 5‐HT6 or 5‐HT7, inhibited luminal 5‐HT‐evoked ΔIsc. Furthermore, luminal cisapride and tegaserod increased Isc to the same extent as did 5‐HT in the presence of indomethacin and TTX. Removal of the submucosa or pretreatment with NOS inhibitors enhanced luminal 5‐HT‐evoked ΔIsc, suggesting that NO synthesized in the submucosa suppresses mucosal anion secretion. NOS1 and NOS2 were immunostained in the submucosal neurons and glial cells respectively. Luminal 5‐HT‐evoked HCO3− secretion was confirmed in vivo, inhibited by co‐perfusion of GR113808, but not by ondansetron.
Conclusions and Implications
A novel apical 5‐HT4‐mediated HCO3− secretory pathway and an NO‐dependent inhibitory mechanism are present in the proximal colon. Luminal 5‐HT‐evoked HCO3− secretion may be important for the maintenance of mucosal integrity by regulating luminal pH.
Reactive oxygen species-induced damage of cells and molecules is one of the mechanisms responsible for the decline in an animal's performance due to heat stress. Mitochondria are the main producers ...of cellular superoxide, a process that is sensitive to proton motive force, and this superoxide production can be decreased by mild uncoupling. We studied the effects of heat stress on the production of mitochondrial superoxide as well as heat stress effects on the expression of avian uncoupling protein (avUCP) and avian A nucleotide translocator (avANT) in skeletal muscles of chicks and young cockerels. Male White Leghorn (Julia) chicks at 16 d and cockerels at 87 d of age were exposed to acute heat stress, 34 degrees C for 18 h, or kept at moderate ambient temperature (25 and 21 degrees C, respectively). There was no difference in mitochondrial superoxide production between heat-exposed and control chicks, whereas significant differences were observed in the case of young cockerels. Greater substrate-independent superoxide production was found in muscle mitochondria from heat-stressed young cockerels. In chicks, neither avUCP nor avANT transcript expression was changed by heat exposure, whereas in young cockerels avUCP transcript was decreased, but avANT transcript level was not changed. Thus, in heat-stressed young cockerels, increased mitochondrial superoxide production was accompanied by downregulation of avUCP. Taken together, these results suggest that exposure of young cockerels to heat stress stimulates mitochondrial superoxide production, possibly via downregulation of avUCP. Chicks with persistent avUCP expression, on the other hand, are relatively better adapted to high temperature. It can be assumed that appropriate expression of avUCP may alleviate overproduction of mitochondrial superoxide and could help birds adapt to oxidative stress resulting from acute heat stress.
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