Dietary daidzein decreases food intake accompanied with delayed gastric emptying in ovariectomized rats.

We previously found that equol, a metabolite of intestinal bacterial conversion from soy isoflavone daidzein, has female-specific anorectic effects. In the present study, we used seven-week-old female ovariectomized (OVX) Sprague Dawley rats to test the hypothesis that the anorectic effect of dietary daidzein may be attributed to delayed gastric emptying. Results suggest that dietary daidzein delays gastric emptying and that it has an anorectic effect with residual gastric contents, but not without gastric contents. Dietary equol significantly decreased daily food intake in the OVX rats without sleeve gastrectomy, but not in those with sleeve gastrectomy, suggesting that the accumulation of food in the stomach is required for the anorectic effect of equol to occur. These results support the hypothesis that the anorectic effect of dietary daidzein is attributed to delayed gastric emptying.

Augmented Reversal of Cisplatin-Induced Delayed Gastric Emptying by Amla (Emblica Officinalis) Fruit Extract in Sprague-Dawley Rats.

Despite the availability of effective antiemetics, control of acute and delayed chemotherapy-induced nausea and vomiting (CINV) is often suboptimal and there is need of an inexpensive and safer alternative. Thus, this study was designed to evaluate the effect of Emblica officinalis Gaertn (Euphorbiaceae) fruit extract (EEEO) on cisplatin-induced delayed gastric emptying in Sprague-Dawley rats so that Emblica officinalis can be clarified for its application in CINV as a potential candidate. Groups I, II, III, IV, and V rats were pretreated orally with 1% carboxymethyl cellulose (CMC, 1 mL/kg), 1% CMC (1 mL/kg), EEEO (250 mg/kg), EEEO (500 mg/kg), and ondansetron (3 mg/kg), respectively, for 5 consecutive days. Then, Group I rats received 0.1 mL of normal saline and Groups II-V rats received 10 mg/kg body weight of cisplatin intraperitoneally. Immediately after that, a test meal (1.5 mL/rat) was administered to each group, and after 30 minutes, rats were euthanized to evaluate the percentage of gastric emptying. EEEO at the specified doses reversed the cisplatin-induced delayed gastric emptying. EEEO (500 mg/kg body weight) pretreatment for 5 days before cisplatin challenge in Group IV rats significantly (p < .05) increased gastric emptying to 74.25% ± 7.19%. Reversal of cisplatin-induced delay in gastric emptying by EEEO (500 mg/kg body weight) in Group IV was significantly (p < .05) comparable to that of the ondansetron treated Group V. EEEO possesses the property to reverse the cisplatin-induced delayed gastric emptying and can be used as an antiemetic for the prevention of CINV.

Glucocorticoids induce gastroparesis in mice through depletion of l-arginine.

Glucocorticoids (GCs) constitute a highly pleiotropic class of drugs predominantly employed in the treatment of inflammatory diseases. In our search for new mechanisms of action, we identified a hitherto unknown effect of GCs in the gastrointestinal tract. We found that oral administration of dexamethasone (Dex) to mice caused an enlargement of the stomach due to the induction of gastroparesis and that this effect was abolished in GR(dim) mice carrying the A458T mutation in the GC receptor (GR). Gastroparesis was unrelated to the enhanced gastric acid secretion observed after Dex treatment, although both effects were mediated by the same molecular mechanism of the GR. Using conditional GR-knockout mice, we could further rule out that GC effects on enterocytes or myeloid cells were involved in the induction of gastroparesis. In contrast, we found that Dex upregulated arginase 2 (Arg2) in the stomach both at the mRNA and protein level. This suggests that GC treatment leads to a depletion of l-arginine thereby impeding the production of nitric oxide (NO), which is required for gastric motility. We tested this hypothesis by supplementing the drinking water of the mice with exogenous l-arginine to compensate for the presumed shortage of this major substrate of NO synthases. Importantly, this measure completely prevented both the enlargement of the stomach and the induction of gastroparesis after Dex treatment. Our findings raise considerations of combining orally applied GCs with l-arginine to improve tolerability of GC treatment and provide a possible explanation for the antiemetic effects of GCs widely exploited in chemotherapy.

Ingluviotomy tube placement for lead-induced crop stasis in the California condor (Gymnogyps californianus).

Six free-flying California condors (Gymnogyps californianus) were diagnosed with acute lead toxicosis that caused crop distension and stasis. Between January 2006 and January 2007, the birds were referred to the Phoenix Zoo in Arizona for emergency treatment. In 5 birds, an ingluviotomy was performed to place a feeding tube from the crop to the proventriculus, which allowed a temporary bypass of the dysfunctional esophagus until normal function and motility were regained. A crop-support pressure bandage was placed in 4 birds to improve crop emptying into the proventriculus and to prevent crop distension. Although chelation therapy is the gold standard treatment for lead toxicosis, severe cases of lead-induced crop stasis are not acutely reversible with pharmaceuticals. In these condors, placement of a feeding tube was deemed prudent to ensure a viable enteric route of nutritional support during the standard treatment and recovery period in acute lead toxicosis with crop stasis.

Effects of corydaline from Corydalis tuber on gastric motor function in an animal model.

The aim of this study was to evaluate the prokinetic and gastric-relaxing effects of the isoquinoline alkaloid corydaline, which was extracted from Corydalis tubers (CT). Corydaline is a marker compound used for quality control of DA-9701, a prokinetic agent formulated from extracts of Pharbitidis semen and Corydalis tuber that is currently in clinical trials in Korea for the treatment of functional dyspepsia (FD). DA-9701 was previously reported to be a potential therapeutic agent for the treatment of abnormalities in gastrointestinal motor function in FD patients; however, the therapeutic effects of corydaline on FD have yet to be demonstrated in an in vivo study. In the current study, oral administration of corydaline not only significantly accelerated gastric emptying in normal rats but also improved delayed gastric emptying to near normal levels. Furthermore, corydaline induced significant gastric relaxation, shifting the pressure-volume curve towards higher volumes compared to controls. These results suggest that corydaline promotes gastric emptying and small intestinal transit and facilitates gastric accommodation.

Effects of mitemcinal (GM-611), an orally active erythromycin-derived prokinetic agent, on delayed gastric emptying and postprandial glucose in a new minipig model of diabetes.

AIMS: This study was conducted to evaluate the suitability of a new minipig model for investigating aspects of diabetes such as delayed gastric emptying and glucose metabolism abnormalities, and to test the effects of mitemcinal (GM-611), an orally active erythromycin-derived motilin receptor agonist, on gastric emptying and postprandial glucose in normal and diabetic minipigs. METHODS AND RESULTS: Intravenous injection of 300 mg/kg streptozotocin (STZ) to 5-week-old minipigs induced moderate hyperglycemia (about 200 mg/dl) for >80 weeks without insulin treatment. Decreased insulin production (P<.05), increased area under the glucose curve (P<.05), and slower glucose disappearance (P<.05) were demonstrated, and there was no severe inhibition of body weight gain, liver failure, or renal failure. Gastric emptying was significantly delayed in diabetic minipigs (P<.05) at 80 weeks, but not at 40 weeks, post-STZ. Oral administration of mitemcinal (5 mg/kg) at 80 weeks accelerated gastric emptying and induced a similar postprandial glucose profile in normal and diabetic minipigs with delayed gastric emptying. CONCLUSIONS: The new diabetic minipig model showed suitability for investigating diabetes, gastric emptying, and plasma glucose excursions. Since delayed gastric emptying and irregular plasma glucose excursions are characteristic of diabetic gastroparesis, the accelerating and regulating effects of mitemcinal on this model add to the existing evidence that mitemcinal is likely to be useful for treating diabetic gastroparesis.

Two-channel gastric pacing with a novel implantable gastric pacemaker accelerates glucagon-induced delayed gastric emptying in dogs.

BACKGROUND: The aim of the current study was to investigate the efficacy of 2-channel gastric electrical stimulation (GES) with a custom-made implantable pacemaker on delayed gastric emptying and gastric dysrhythmia induced by glucagon in dogs. METHODS: Six dogs were studied in 4 randomized session (saline, glucagon, glucagon with single-channel or 2-channel GES). GES was applied via the first pair of electrodes for single-channel GES or the first and third pairs of electrodes for 2-channel GES. Gastric emptying was assessed for 90 minutes and gastric slow waves were recorded at the same time. RESULTS: Both single-channel and 2-channel GES improved gastric dysrhythmia (P < .05 vs glucagon session). Two-channel GES but not single-channel GES improved glucagon-induced delayed gastric emptying at 30 minutes, 45 minutes, 60 minutes, 75 minutes, and 90 minutes. CONCLUSION: Two-channel GES with a novel implantable pacemaker is more efficient and effective than single-channel GES in improving delayed gastric emptying induced by glucagon. This implantable multipoint pacemaker may provide a new option for treatment of gastric motility disorders.

Gastric stimulation is effective in reversing vasopressin induced gastroparesis.

UNLABELLED: The aim of this study was to determine the most effective current parameters reversing vasopressin (VP) induced gastroparesis by gastric electrical stimulation IGES). METHODS: Twenty male healthy Wistar rats were included into the study (weight 227 +/- 24 g). Animals were subjected to gastric fistula placement and implantation of two monopolar electrodes for EGG-studies and GES. After 5 days of recovery VP was applied (terlipressin 0.1 mg/kg i.p.) The gastric motility was measured by means of balloon introduced into the stomach through the fistula. The gastric electrical and motor activity were recorded by the PowerLab/8SP system and software. Electrical signals were cleared by 3000 AC/DC differential amplifier A-M System Inc. Gastric electrical stimulation (GES) was generated by Zimmer stimulator SINUS5. The following currents: S01 (monopolar): ampl 2.2 mA, freq 29 Hz, on/off 1 s / 10 s; S02 (bipolar): ampl 2.2 mA, freq 29 Hz, on/off 1s/10s: S03 (monopolar): ampl 2.2 mA, freq 0.5 Hz: S04 (monopolar): ampl 2.2 mA, freq 34 Hz, on/off 5.5 s/15 s were used. RESULTS: The phasic contractions almost disappeared and amplitude decreased from 12 +/- 5 to 2.9 +/- 1.5 cm H20. The motility index decreased from 276,3 +/- 76.4 to 154.6 +/- 63 cm H2O x s/min. GES S01-S04 increased motility index to: 167.6 +/- 60.8: 155.1 +/- 89.3; 170.3 +/- 92.3: 301.9 +/- 70.5 cm H2O x s/min respectively. The frequency of gastric slow wave increased from 0.04 +/- 0.02 to 0.07 +/- 0.02 Hz after VP administration. GES S01-S04 reversed VP induced increase of slow wave frequency to 0.06 +/- 0.02, 0.055 +/- 0.02, 0.06 +/- 0.01 and 0.04 +/- 0.02 Hz, respectively. CONCLUSIONS: This effectiveness of local GES and the pressure pattern of induced gastroparesis suggest peripheral complex inhibitory-excitatory action of vasopressin on gastric smooth muscles. The mechanism of this action may involve the enteric nervous system, gastric and vasal smooth muscles. The most effective in reversing VP induced functional gastroparesis is high frequency current applied in timing of the natural slow wave.

[Effect of acupuncture on the restrained state of stomach after injecting TFP in zusanli point].

A model of the reducible movement of stomach in a big mouse was set up by injecting solution of 654-2. At first, the state of stomach movement was proved to be improved by acupuncture. After that, the activity of CaM in Zusanli point was lost by injecting TFP and effect of acupuncture on the stomach movement was studied. The result showed that the effect of acupuncture was abolished during manipulating the needles for 5 minutes. But retaining the needle for 25 minutes, the effect of acupuncture was recovered gradually. It indicates that the activity of Ca-CaM compounds may be of the key factor of acupuncture effect and one of the important links of the functional activity of meridians and collaterals.