Chihiro Tsutsui

Coordination of motilin and ghrelin regulates the migrating motor complex of gastrointestinal motility in Suncus murinus

Motilin and ghrelin are the gastrointestinal (GI) hormones released in a fasting state to stimulate the GI motility of the migrating motor complex (MMC). We focused on coordination of the ghrelin/motilin family in gastric contraction in vivo and in vitro using the house musk shrew (Suncus murinus), a ghrelin- and motilin-producing mammal. To measure the contractile activity of the stomach in vivo, we recorded GI contractions either in the free-moving conscious or anesthetized S. murinus and examined the effects of administration of motilin and/or ghrelin on spontaneous MMC in the fasting state. In the in vitro study, we also studied the coordinative effect of these hormones on the isolated stomach using an organ bath. In the fasting state, phase I, II, and III contractions were clearly recorded in the gastric body (as observed in humans and dogs). Intravenous infusion of ghrelin stimulated gastric contraction in the latter half of phase I and in the phase II in a dose-dependent manner. Continuous intravenous infusion of ghrelin antagonist (d-Lys3-GHRP6) significantly suppressed spontaneous phase II contractions and prolonged the time of occurrence of the peak of phase III contractions. However, intravenous infusion of motilin antagonist (MA-2029) did not inhibit phase II contractions but delayed the occurrence of phase III contractions of the MMC. In the in vitro study, even though a high dose of ghrelin did not stimulate contraction of stomach preparations, ghrelin administration (10(-10)-10(-7) M) with pretreatment of a low dose of motilin (10(-10) M) induced gastric contraction in a dose-dependent manner. Pretreatment with 10(-8) M ghrelin enhanced motilin-stimulated gastric contractions by 10 times. The interrelation of these peptides was also demonstrated in the anesthetized S. murinus. The results suggest that ghrelin is important for the phase II contraction and that coordination of motilin and ghrelin are necessary to initiate phase III contraction of the MMC.

Primary structure, tissue distribution, and biological activity of chicken motilin receptor

Motilin is a peptide hormone involved in gastrointestinal motility. GPR38, initially cloned as an orphan receptor, is now considered a specific receptor for motilin. Previously, molecular characterization of the motilin receptor had only been performed in mammalian and fish species. In this study, we cloned cDNA for chicken motilin receptor from the duodenum and characterized its primary structure, tissue distribution, and biological activity. The cDNA encoded 349 amino acids showing significant overall sequence identity to mammalian motilin receptors. Chicken motilin increased intracellular Ca2+ concentration in human embryonic kidney (HEK) 293 cells transiently expressing the recombinant chicken motilin receptor. Comparison of the cDNA sequence with the genomic sequence of chicken motilin receptor revealed that the chicken motilin receptor gene consists of two exons separated by an intron. Real-time PCR analysis showed that chicken motilin receptor mRNA is expressed in a wide range of tissues in 21-day-old chickens, with markedly high levels in the proventriculus, duodenum, and oviduct. The expression levels of the mRNA in the proventriculus and duodenum were highest just before hatching and rapidly decreased during post-hatch development. These results suggest that chicken motilin receptor is largely involved in gastrointestinal functions at pre- and post-hatch periods through an intracellular signaling pathway accompanied by an increase in Ca2+ levels.

Molecular identification of GHS-R and GPR38 in Suncus murinus

We previously identified ghrelin and motilin genes in Suncus murinus (suncus), and also revealed that motilin induces phase III-like strong contractions in the suncus stomach in vivo, as observed in humans and dogs. Moreover, repeated migrating motor complexes were found in the gastrointestinal tract of suncus at regular 120-min intervals. We therefore proposed suncus as a small laboratory animal model for the study of gastrointestinal motility. In the present study, we identified growth hormone secretagogue receptor (GHS-R) and motilin receptor (GPR38) genes in the suncus. We also examined their tissue distribution throughout the body. The amino acids of suncus GHS-R and GPR38 showed high homology with those of other mammals and shared 42% amino acid identity. RT-PCR showed that both the receptors were expressed in the hypothalamus, medulla oblongata, pituitary gland and the nodose ganglion in the central nervous system. In addition, GHS-R mRNA expressions were detected throughout the stomach and intestine, whereas GPR38 was expressed in the gastric muscle layer, lower intestine, lungs, heart, and pituitary gland. These results suggest that ghrelin and motilin affect gut motility and energy metabolism via specific receptors expressed in the gastrointestinal tract and/or in the central nervous system of suncus.

Myenteric neural network activated by motilin in the stomach of Suncus murinus (house musk shrew)

Background  It has been shown in human and canine studies that motilin, a gastroprokinetic hormone, induces gastric phase III contractions via the enteric nervous; however, the center of motilin action in the stomach has not been clearly revealed. In the present study, we investigated the neural pathway of motilin‐induced gastric contraction by using Suncus murinus, a new animal model for motilin study.

Healing burns using atmospheric pressure plasma irradiation

An experiment testing the effects of plasma irradiation with an atmospheric-pressure plasma (APP) reactor on rats given burns showed no evidence of electric shock injuries upon pathology inspection of the irradiated skin surface. In fact, the observed evidence of healing and improvement of the burns suggested healing effects from plasma irradiation. The quantities of neovascular vessels in the living tissues at 7 days were 9.2 ? 0.77 mm?2 without treatment and 18.4 ? 2.9 mm?2 after plasma irradiation.

Treatment of cardiac disease by inhalation of atmospheric pressure plasma

The use of inhaled plasma, generated by an atmospheric-pressure plasma (APP) reactor, in a rat myocardial infarction (MI) model resulted in an increased saturation pulse oxygen (SpO2) level in the blood, which suggests that this method can be beneficial in restoring heart function following cardiac ischemia. Additionally, in vivo blood pressure decreased from 89/81 to 73/60 mmHg in the abdominal aorta during plasma inhalation. The nitric oxide (NO) concentration in the abdominal aorta increased after 20 s of plasma inhalation, reaching a maximum value at about 160 s and gradually decreased thereafter.

Fat Liquefaction of Adipose Tissue Using Atmospheric-Pressure Plasma Irradiation

The liquefaction of fat in adipose tissue for potential medical applications was achieved by direct irradiation using an atmospheric-pressure plasma source and a catheter-type apparatus. When fat was irradiated with plasma generated from a catheter tip, it was liquefied through ozonolysis, although little production and diffusion of ozone originating from the collision/ionization of gas molecules was observed in preliminary experiments. Furthermore, surface damage to fat cells, such as thermal carbonization or electric shock injuries, was not observed.

Measurement of Contractile Activity in Small Animal's Digestive Organ by Carbon Nanotube-Based Force Transducer

A carbon nanotube (CNT)-based force transducer designed to be embedded in the body of a live animal was fabricated and implanted into the stomach of a rat omit to measure contractile movement. The transducer comprised dispersed poly(ethylene glycol)-grafted multiwalled CNTs applied to a comb-like Au-electrode formed on a poly(dimethylsiloxane) sheet. The implanted rat was injected with acetylcholine to induce muscular contractions and changes in the resistance of the transducer were measured. Such changes arise owing to strain in the CNT network upon distortion. The measured resistance change was found to be proportional to the concentration of injected acetylcholine.

Noninvasive measurement of fetal augmentation index by fetal aortic diameter pulse and flow velocity waveforms

Objective. To study fetal systemic arterial stiffness in normal fetuses and compromised fetuses who had umbilical placental insufficiency (UPI). Design. Prospective study. Setting. University departments. Sample. A total of 118 normal fetuses (21–40 weeks) and 55 fetuses (UPI group) with evidence of potential compromise (high umbilical artery pulsatility index). Methods. A new real‐time noninvasive measurement system based on a combined Doppler ultrasound and echo‐tracking system was used as a measure of aortic/systemic arterial stiffness. The augmentation index (AI) of the fetal thoracic descending aorta was measured by using simultaneous measurements of diameter pulse and flow velocity waveforms. Main Outcome Measure. Augmentation index as a measure of stiffness. Results. In normal fetuses, successful measurements for obtaining the AI were achieved in 103 of 118 fetuses. In the normal group, the AI, as well as placental resistance, decreased during the second trimester; in contrast, an increase in the AI was observed during the third trimester. Using the AI values from the normal group, the UPI group was divided into two subgroups: 29 fetuses with a normal AI and 26 fetuses with a high AI. The clinical outcome was significantly worse in the latter subgroup compared with the normal subgroup. Conclusions. The increase of afterload caused by a high umbilical placental resistance was associated with a decrease of aortic distensibility in the compromised fetuses, suggesting an alteration of aortic wall structure.