The herbal preparation, STW5-II, reduces proximal gastric tone and stimulates antral pressures in healthy humans.

BACKGROUND: The herbal preparation, STW5-II, improves upper gastrointestinal symptoms, including abdominal fullness, early satiation, and epigastric pain, in patients with functional dyspepsia, and in preclinical models decreases fundic tone and increases antral contractility. The effects of STW5-II on esophago-gastric junction pressure, proximal gastric tone and antropyloroduodenal pressures, disturbances of which may contribute to symptoms associated with disorders of gut-brain interaction, including functional dyspepsia, in humans, have, hitherto, not been evaluated. METHODS: STW5-II or placebo (matched for color, aroma, and alcohol content) were each administered orally, at the recommended dose (20 drops), to healthy male and female volunteers (age: 27 ± 1 years) in a double-blind, randomized fashion, on two separate occasions, separated by 3-7 days, to evaluate effects on (i) esophago-gastric junction pressures following a standardized meal using solid-state high-resolution manometry (part 1, n = 16), (ii) proximal gastric volume using a barostat (part 2, n = 16), and (iii) antropyloroduodenal pressures assessed by high-resolution manometry (part 3, n = 18), for 120 min (part 1) or 180 min (parts 2, 3). KEY RESULTS: STW5-II increased maximum intrabag volume (ml; STW5-II: 340 ± 38, placebo: 251 ± 30; p = 0.007) and intrabag volume between t = 120 and 180 min (p = 0.011), and the motility index of antral pressure waves between t = 60 and 120 min (p = 0.032), but had no effect on esophago-gastric junction, pyloric, or duodenal pressures. CONCLUSIONS & INFERENCES: STW5-II has marked region-specific effects on gastric motility in humans, which may contribute to its therapeutic efficacy in functional dyspepsia.

Bmi1 marks gastric stem cells located in the isthmus in mice.

In the mammalian stomach, the isthmus has been considered as a stem cell zone. However, various locations and proliferative activities of gastric stem cells have been reported. We focused here on the stem cell marker Bmi1, a polycomb group protein, aiming to elucidate the characteristics of Bmi1-expressing cells in the stomach and to examine their stem cell potential. We investigated the Bmi1-expressing cell lineage in Bmi1-CreERT; Rosa26-YFP, LacZ or Rosa26-Confetti mice. We examined the in vivo and ex vivo effects of Bmi1-expressing cell ablation by using Bmi1-CreERT; Rosa26-iDTR mice. The Bmi1 lineage was also traced during regeneration after high-dose tamoxifen-, irradiation- and acetic acid-induced mucosal injuries. In the lineage-tracing experiments using low-dose tamoxifen, Bmi1-expressing cells in the isthmus of the gastric antrum and corpus provided progeny bidirectionally, towards both the luminal and basal sides over 6 months. In gastric organoids, Bmi1-expressing cells also provided progeny. Ablation of Bmi1-expressing cells resulted in impaired gastric epithelium in both mouse stomach and organoids. After high-dose tamoxifen-induced gastric mucosal injury, Bmi1-expressing cell lineages expanded and fully occupied all gastric glands of the antrum and the corpus within 7 days after tamoxifen injection. After irradiation- and acetic acid-induced gastric mucosal injuries, Bmi1-expressing cells also contributed to regeneration. In conclusion, Bmi1 is a gastric stem cell marker expressed in the isthmus of the antrum and corpus. Bmi1-expressing cells have stem cell potentials, both under physiological conditions and during regeneration after gastric mucosal injuries. Copyright © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Mechanisms of PTHrP-induced inhibition of smooth muscle contractility in the guinea pig gastric antrum.

BACKGROUND: Parathyroid hormone-related protein (PTHrP) that causes hypercalcemia of malignancy appears to function as an endogenous smooth muscle relaxant. For example, PTHrP released upon bladder wall distension relaxes detrusor smooth muscle to accommodate urine. Here, we explored mechanisms underlying PTHrP-induced suppression of the smooth muscle contractility in the gastric antrum that also undergoes a passive distension. METHODS: Effects of PTHrP on phasic contractions and electrical slow waves in the antral smooth muscle of the guinea pig stomach were studied using isometric tension and intracellular microelectrode recordings, respectively. Fluorescent immunohistochemistry was also carried out to identify the distribution of PTH/PTHrP receptors. KEY RESULTS: Parathyroid hormone-related protein (1-100 nM) reduced the amplitude of phasic contractions and the basal tension. Nω -nitro-l-arginine (L-NA, 100 µM), a nitric oxide (NO) synthase inhibitor, or 1H-[1,2,4]oxadiazolo-[4, 3-a]quinoxalin-1-one (ODQ, 10 µM), a guanylate cyclase inhibitor, diminished the PTHrP (10 nM)-induced reduction in the amplitude of phasic contractions. SQ22536 (300 µM), an adenylate cyclase inhibitor, attenuated the PTHrP-induced reduction in basal tension. The combination of ODQ (10 µM) and SQ22536 (300 µM) inhibited the PTHrP-induced reductions in both phasic contractions and basal tension. PTHrP (100 nM) had no inhibitory effect on the electrical slow waves in the antral smooth muscle. PTH/PTHrP receptors were expressed in cell bodies of PGP9.5-positive neurons in the myenteric plexus. CONCLUSIONS & INFERENCES: Parathyroid hormone-related protein exerts its inhibitory actions on the antral smooth muscle via both nitric oxide-cyclic guanosine monophosphate (NO-cGMP) and cyclic adenosine monophosphate (AMP) pathways. Thus, PTHrP may act as an endogenous relaxant of the gastric antrum employing the two complementary signaling pathways to ensure the adaptive relaxation of stomach.

Auricular vagal nerve stimulation ameliorates burn-induced gastric dysmotility via sympathetic-COX-2 pathways in rats.

BACKGROUND: Severe burn injury has been demonstrated to delay gastric emptying. The aim of this study was to investigate effects and cellular mechanisms of auricular electroacupuncture (AEA) at the acupoints innervated by the auricular branch of vagus nerve on burn-induced gastric dysmotility in rats. METHODS: Propranolol (ß-adrenoceptor antagonist) was injected intraperitoneally after the rats underwent burn injury. All experiments were performed 6 h following burn/sham burn injury. AEA was performed at bilateral auricular acupoints for 45 min. Electrocardiogram was recorded for 30 min. Plasma hormones were measured; cyclooxygenase (COX)-2 expressions in gastric tissue were measured using western blotting and real-time RT-PCR. KEY RESULTS: (i) Burn injury delayed gastric emptying (p = 0.006) and AEA increased gastric emptying by 49% (p = 0.045). (ii) Burn injury evoked a significant elevation in plasma noradrenaline, which was suppressed by AEA. (iii) Burn injury significantly increased protein and mRNA expressions of COX-2 in gastric fundus and antrum. AEA suppressed burn-induced increase in protein expressions, but not mRNA expressions of COX-2. CONCLUSIONS & INFERENCES: Burn injury delays gastric emptying by up-regulating COX-2 attributed to sympathetic overactivity. AEA improves burn-induced delay in gastric emptying, possibly mediated via the sympathetic-COX-2 pathway.

Traditional Chinese medicine Zhiqiao-Houpu herb-pair induce bidirectional effects on gastric motility in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Zhiqiao-Houpu herb-pair (ZQHPHP), composed of Fructus Aurantii (Zhiqiao [ZQ] in Chinese) and Magnolia officinalis (Houpu [HP] in Chinese), is a traditional herbal formula that has been extensively used for treating gastrointestinal motor dysfunction. The aim of the study was to evaluate the effect and possible mechanism of ZQHPHP on gastric emptying (GE) and gastric antral smooth muscle contractility (GASMC). MATERIALS AND METHODS: This study includes four parts: (a) study of ZQHPHP's effect on GE; (b) study of ZQHPHP's effect on gastric antral smooth muscle contractility (GASMC); (c) comparing the effects of ZQHPHP, ZQ and HP on GASMC; (d) study of antagonists or agonists on ZQHPHP-induced GASMC. A test meal of Evans blue was adopted to estimate GE in rats. A polygraph was used to measure GASMC in rats. RESULTS: The in vivo experiments demonstrated that, at the doses of 10mg/kg bw and 20mg/kg bw, ZQHPHP could promote GE. While, at the higher dose of 30 mg/kg bw, ZQHPHP delayed the GE. From the in vitro experiments we found that ZQHPHP (3-10 µg/ml) concentration-dependently increased the mean amplitude of contractions in the antral circular strip compared to untreated controls. While, in the concentration of 30 µg/ml, ZQHPHP prohibited GASMC. Besides, atropine blocked the stimulatory effect of ZQHPHP on GASMC and norepinephrine partly prohibited the stimulatory effect of ZQHPHP on GASMC, whereas isoproterenol showed no effect. From the in vitro experiment, we also found that ZQ and HP used together can synergistically increase gut motor. CONCLUSIONS: The experiment indicated that ZQHPHP could induce bidirectional regulation on gastric motility. ZQ and HP used together can synergistically increase gut motor at a certain dosage. Lower dosage of ZQHPHP increases gastric motility, while higher dosage produces inhibition. In addition, the improvement of gastric motility by ZQHPHP is predominantly involved with muscarinic receptors and secondarily with alpha-receptors.

Rikkunshito induces gastric relaxation via the ß-adrenergic pathway in Suncus murinus.

BACKGROUND: Rikkunshito (RKT) is a gastroprotective herbal medicine. In this study, we investigated the role of RKT in the relaxation of the gastric body (fundus and corpus) and antrum. METHODS: We used Suncus murinus, a unique small model animal with similar gastrointestinal motility to humans and dogs. RKT was added at 0.1, 1.0, and 5.0 mg/mL to induce relaxation in vitro; the outcome measure was the intensity of relaxation. The number of spontaneous antral contractions in the absence or the presence of RKT was also counted. KEY RESULTS: Rikkunshito induced the relaxation of the gastric body and antrum and decreased the number of spontaneous antral contractions in a dose-dependent manner. The responses to RKT (1.0 mg/mL) were not affected by pretreatment with atropine, N-nitro-l-arginine methyl ester, ritanserin, or ondansetron. On the other hand, timolol almost completely reversed the relaxation induced by RKT (1.0 mg/mL) on the gastric body and antrum and the occurrence of the spontaneous antral contractions. Both butoxamine, a ß(2) -adrenoreceptor antagonist, and L 748337, a ß(3) -adrenoreceptor antagonist, but not CGP 20712, a ß(1) -adrenoreceptor antagonist, significantly reversed the RKT-induced (1.0 mg/mL) gastric relaxation. CONCLUSIONS & INFERENCES: These results indicate that RKT stimulates and modulates gastric relaxation through ß(2) - and ß(3) -adrenergic, but not ß(1) -adrenergic, pathways in S. murinus.

Different antibiotic susceptibility between antrum and corpus of the stomach, a possible reason for treatment failure of Helicobacter pylori infection.

AIM: To assess whether antibiotic resistance varies between the antrum and corpus of the stomach of patients that are either Helicobacter pylori (H. pylori) therapy-naive or pre-treated. METHODS: H. pylori strains were isolated from antrum and corpus biopsies from 66 patients that received a diagnostic gastroduodenoscopy for variant clinical indications. Antimicrobial susceptibility to amoxicillin, clarithromycin, tetracycline, metronidazole, levofloxacin and rifabutin was tested with the E-test method on Iso-Sensitest agar with 10 vol% defibrinated horse blood. In patients with a different antibiotic susceptibility pattern between the isolates from the antrum and corpus, DNA fingerprinting via random amplified polymorphic DNA analysis was performed to detect differences among DNA patterns of H. pylori isolates. RESULTS: Primary, secondary and tertiary resistance to clarithromycin was 6.9%, 53.8% and 83.3%, retrospectively. Metronidazole and levofloxacin resistance also increased according to the number of previous treatments (17.2%, 69.2%, 83.3%; 13.8%, 23.1%, 33.3%). Tertiary resistance to rifabutin was detected in 12.5% of patients. In none of the 66 patients a resistance against amoxicillin or tetracycline was detectable. Discordant antibiotic susceptibility between antrum and corpus isolates for different antibiotics was seen in 15.2% (10/66) of the patients. Two out of those ten patients were naive to any H. pylori antibiotic treatment. The remaining eight patients previously received at least one eradication therapy. DNA fingerprinting analysis revealed no substantial differences among DNA patterns between antrum and corpus isolates in the majority of patients suggesting an infection with a single H. pylori strain. CONCLUSION: Different antibiotic susceptibility between antrum and corpus biopsies is a common phenomenon and a possible explanation for treatment failure. Resistant H. pylori strains may be missed if just one biopsy from one anatomic site of the stomach is taken for H. pylori susceptibility testing.

Simo decoction promotes contraction of antral circular smooth muscle mainly via muscarinic M3 receptor.

ETHNOPHARMACOLOGICAL RELEVANCE: Simo Decoction (SMD), a traditional Chinese medicine, included four elements, such as Fructus aurantii, Radix aucklandiae, Semen arecae and Radix linderae. It has been used to improve gastrointestinal dysmotility in clinical practice for a long history in China. However, the explicit mechanisms are unclear. The aim of this study was to investigate the effect of SMD on contractions of antral circular smooth muscle strips of Sprague-Dawley (SD) rats and its underlying mechanism. MATERIALS AND METHODS: The antral circular strips were prepared in the organ bath under baseline or to be incubated with muscarinic receptor antagonist atropine (10(-6)M), muscarinic M3 receptor antagonist 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) (0.4×10(-6)M), muscarinic M2 receptor antagonist gallamine (10(-6)M), adrenergic receptor agonist adrenaline (10(-7)M), exogenous nitric oxide (NO) donor l-arginine (10(-4)M), nicotinic receptor antagonist hexamethonium chloride (10(-4)M) and Ca(2+) channel antagonist nifedipine (30nM), and consecutive concentrations of SMD were added to the bath to observe the strip responses. As a control, the responses of strips after administration with the same volume of Krebs solution as SMD were also noted. The strip responses to acetylcholine (10(-7)-10(-3)M) were also noted in organ bath to compare with SMD-induced contraction. RESULTS: SMD dose-dependently evoked hypercontractility of antral circular strips, and the maximal contractile effect of circular smooth muscle induced by SMD was significantly higher than that induced by acetylcholine (10(-3)M). The responses of antral circular strips to SMD were completely antagonized by atropine, 4-DAMP or 4-DAMP+gallamine, but partly inhibited by gallamine and partly suppressed by adrenaline, l-arginine, hexamethonium chloride and nifedipine. CONCLUSIONS: SMD promotes contractions of antral circular strips in rats mainly via activation of muscarinic M3 receptor, but partly via activation of muscarinic M2 receptor, Ca(2+) channel and nicotinic receptor, inhibition of adrenergic receptor and releasing of NO.

The effect of Taraxacum officinale on gastric emptying and smooth muscle motility in Rodents.

BACKGROUND: Taraxacum officinale (TO) is a traditional herbal medicine that has been widely used for abdominal illnesses. However, the efficacy and the mechanism of TO on gastric emptying (GE) and smooth muscle motility are unknown. METHODS: Ethyl acetate fraction (EA), n-butanol fraction (BF), and aqueous fraction (AF) were prepared in succession from 70% ethanol extract (EE) of TO using solvent polarity chromatography. Phenol red meal was adopted to estimate GE in mice. A polygraph was used to measure the smooth muscle motility in rats. KEY RESULTS: The percentage of GE was 48.8 ± 6.1% (vehicle control), 75.3 ± 6.5% (cisapride positive control), 68.0±6.7% (EE), 53.3±6.0% (EA), 54.1±6.3% (AF), and 86.0±6.5% (BF). Thus, BF was determined to be most effective in accelerating GE. This stimulatory effect of BF on GE was also supported by the observation that BF increased spontaneous contraction of gastric fundus and antrum and decreased the spontaneous motility of pyloric sphincter in vitro. Atropine blocked the stimulatory effect of BF on GE, whereas phentolamine and propranolol had no effect. CONCLUSIONS & INFERENCES: BF seems to be a promising prokinetic agent. BF-induced increase in the contraction of fundus and antrum contributes to an increase in the intra-gastric pressure. BF-induced decrease in the motility of pyloric sphincter contributes to a decrease in the resistance of food from the stomach to the small intestine. The acceleration of GE by BF is likely to be exerted through cholinergic stimulation.

Monosodium glutamate raises antral distension and plasma amino acid after a standard meal in humans.

The consumption of monosodium glutamate (MSG) is advocated to elicit physiological and metabolic effects, yet these effects have been poorly investigated directly in humans and in particular in the postprandial phase. Thirteen healthy adults were supplemented for 6 days with a nutritional dose of MSG (2 g) or sodium chloride (NaCl) as control, following a crossover design. On the 7th day, they underwent a complete postprandial examination for the 6 h following the ingestion of the same liquid standard meal (700 kcal, 20% of energy as [(15)N]protein, 50% as carbohydrate, and 30% as fat) supplemented with MSG or NaCl. Real-ultrasound measures of antral area indicated a significant increased distension for the 2 h following the meal supplemented with MSG vs. NaCl. This early postprandial phase was also associated with significantly increased levels of circulating leucine, isoleucine, valine, lysine, cysteine, alanine, tyrosine, and tryptophan after MSG compared with NaCl. No changes to the postprandial glucose, insulin, glucagon-like peptide (GLP)-1, and ghrelin were noted between MSG- and NaCl-supplemented meals. Subjective assessments of hunger and fullness were neither affected by MSG supplementation. Finally, the postprandial fate of dietary N was identical between dietary conditions. Our findings indicate that nutritional dose of MSG promoted greater postprandial elevations of several indispensable amino acids in plasma and induced gastric distension. Further work to elucidate the possible sparing effect of MSG on indispensable amino acid first-pass uptake in humans is warranted. This trial was registered at clinicaltrials.gov as NCT00862017.

In vitro and in vivo anti-Helicobacter/Campylobacter activity of the aqueous extract of Enantia chlorantha.

The aqueous extract of Enantia chlorantha Oliver (Annonaceae) stem bark, a plant widely used in Cameroon for the traditional treatment of gastritis and stomach problems, was assessed for in vitro and in vivo anti-Helicobacter/Campylobacter properties using the well diffusion assay, agar dilution assay, and killing rate determination. The in vitro activity was dose-dependent, and the same antimicrobial parameters (MAQ = 0.63 mg; MIC = 0.39 mg/mL; MBC = 1.56 mg/mL; ET(100) = 8 h) were obtained for both H. pylori and C. jejuni/coli. When the plasma active principle concentration equivalence was determined in vitro using plasma from rats exposed to a single dose (3000 mg/kg) of the extract, the peak absorption of E. chlorantha active principle against H. pylori occurred at 2 h. Plasma activity was nil 8 h after extract administration. The in vivo H. pylori eradication potency of the extract was assessed using mice infected with H. pylori. Antral mucus sample cultures from mice treated with E. chlorantha extract (500 and 1000 mg/kg for 3 days) did not yield any growth. The results suggest that in addition to its in vitro activity, E. chlorantha water extract also possesses in vivo antibiotic effects against H. pylori.

[Effect of method of soothing liver and regulating qi on expression of gastrin and somatostatin in hypothalamus, castric antrum of functional dyspepsia rats].

OBJECTIVE: To explore the effects of the method of soothing the liver and regulating qi on expression of gastrin and somatostatin in hypothalamus and gastric antrum of functional dyspepsia model rats. METHOD: The 32 rats were randomly divided into normal group, model group, Chaihu Shugansan group and domperidone group (n = 8). The functional dyspepsia model was established by constantly squeezing their tails and mean while saline, Chaihu Shugansan decoction and domperidone suspension were administered respectively to 4 groups by gavage. The expression of gastrin and somatostatin in hypothalamus and gastric antrum of rats by immunohistochemical were detected 3 weeks later. RESULT: The expression of GAS in the hypothalamus and gastric antrum of model group were less than those of normal group (P < 0.05, P < 0.01), while the expression of SS in the hypothalamus and gastric antrum in Model group were significantly increased than those of normal group (P < 0.01). The expression of GAS and SS in gastric antrum of Chaihu Shugansan group and domperidone group were increased and decreased respectively, and the differences were significant (P < 0.05, P < 0.01). There were no obvious difference about expression of GAS, SS in the hypothalamus between domperidone group and model group. GAS expression in hypothalamus of Chaihu Shugansan group were increased than those of normal group but there was no obvious difference in SS expression in hypothalamus between Chaihu Shugansan group and model group. CONCLUSION: The method of soothing the liver and regulating qi can increase GAS expression in central and peripheral and decrease SS expression in peripheral gastric antrum, which may be one of its therapeutic mechanisms on functional dyspepsia.

Acupuncture modulates mechanical responses of smooth muscle produced by transmural nerve stimulation in gastric antrum of genetically hyperglycemic rats.

Effects of acupuncture treatment on mechanical responses produced by transmural nerve stimulation (TNS) and acetylcholine (ACh) were investigated in circular smooth muscle preparations isolated from the antrum of the stomach of genetically hyperglycemic rats. While control rats had blood glucose levels of about 140 mg/dl, this was approximately tripled in the genetically hyperglycemic rats, but only doubled in the acupuncture treated genetically hyperglycemic rats. Antrum smooth muscle produced phasic contractions spontaneously, with a similar frequency and amplitude in the three groups of rats. Effects of atropine and Nomega-nitro-L-arginine (L-NA) on TNS-induced responses revealed that in the antrum smooth muscle of the control rats, cholinergic excitatory, non-adrenergic non-cholinergic excitatory (NANCE), nitrergic inhibitory and off-responses produced projections: the last projection was considered to be non-adrenergic non-cholinergic non-nitrergic (NANCNN) in nature. In genetically hyperglycemic rats, nitrergic and NANCNN projections were enhanced and NANCE projections were absent. Acupuncture treated genetically hyperglycemic rats showed a reduction of NANCNN projection and enhancement of cholinergic projection, with no alteration to nitrergic projection, but a recovery of NANCE projection. ACh elicited inhibitory responses at low concentrations (1-30 nM) and excitatory responses at high concentrations (100-300 nM), in the three groups of rats. L-NA converted the ACh-induced inhibitory responses to excitatory responses. Immunohistochemical examination indicated no significant difference in the distribution of c-Kit expressing cells in the antrum smooth muscle from the three groups of rats. The results indicated that in antral smooth muscle, hyperglycemia was associated with enhanced activity in nitrergic and NANCNN projections and attenuation of NANCE projections, and that acupuncture treatment caused both a reduced blood glucose level and attenuated NANCNN projections. In genetically hyperglycemic rats, cholinergic responses were enhanced by acupuncture, possibly due to the enhanced cholinergic projections, with no change in the sensitivity of postjunctional muscarinic receptors to ACh.

[Influence of Qingxiang San on substance P, somatostatin in rats model with the spleen and stomach wet heat syndrome].

OBJECTIVE: To observe the influence of Qingxiang San (QS) on substance P (SP), somatostatin (SS) in rats model of spleen and stomach wet heat syndrome. METHODS: 24 rats were divided into 3 groups (each group 8 rats) randomly: the normal control group (NCG), wet heat group (WHG), QS group (QSG). We set up the spleen and stomach wet heat syndrome of rats model by the composite factors such as greasy and sweet food, wet and hot environment, pathogen and so on. Then the contents of SP, SS were detected by radioimmuno assay. RESULTS: The content of SP, SS in WHG were obviously lower than NCG (P<0.01); QSG compared with WHG, the content of SP, SS increased (P<0.01); The content of SP obviously increased when QSG compared with NCG (P<0.01); About the content of SS, there was no significant difference between QSG and NCG (P>0.05), illustrating that QS can increase the content of SP, SS which had decreased. CONCLUSION: QS can regulate the content of SP and SS and increase them which had decreased.

Identification, physiological actions, and distribution of VYRKPPFNGSIFamide (Val1)-SIFamide) in the stomatogastric nervous system of the American lobster Homarus americanus.

In this study, the peptide VYRKPPFNGSIFamide (Val(1)-SIFamide) was identified in the stomatogastric nervous system (STNS) of the American lobster, Homarus americanus, using matrix-assisted laser desorption/ionization-Fourier transform mass spectrometry (MALDI-FTMS). When bath-applied to the stomatogastric ganglion (STG), synthetic Val(1)-SIFamide activated the pyloric motor pattern, increasing both burst amplitude and duration in the pyloric dilator (PD) neurons. To determine the distribution of this novel SIFamide isoform within the lobster STNS and neuroendocrine organs, a rabbit polyclonal antibody was generated against synthetic Val(1)-SIFamide. Whole-mount immunolabeling with this antibody showed that this peptide is widely distributed within the STNS, including extensive neuropil staining in the STG and commissural ganglia (CoGs) as well as immunopositive somata in the CoGs and the oesophageal ganglion. Labeling was also occasionally seen in the pericardial organ (PO), but not in the sinus gland. When present in the PO, labeling was restricted to fibers-of-passage and was never seen in release terminals. Adsorption of the antibody by either Val(1)-SIFamide or Gly(1)-SIFamide abolished all Val(1)-SIFamide staining within the STNS, including the STG neuropil, whereas adsorption by other lobster neuropeptides had no effect on immunolabeling. These data strongly suggest that the staining we report is a true reflection of the distribution of this peptide in the STNS. Collectively, our mass spectrometric, physiological, and anatomical data are consistent with Val(1)-SIFamide serving as a locally released neuromodulator in the lobster STG. Thus, our study provides the first direct demonstration of function for an SIFamide isoform in any species.

[Effect of zu' ai weitai granule on substance P, vasoactive intestinal peptide, calcitonin gene-related peptide of precancerous lesion of gastric antrum in rats].

OBJECTIVE: To explore the relationship between precancerous lesions of gastric antrum and substance P (SP) , vasoactive intestinal peptide ( VIP) , calcitonin gene-related peptide (CGRP), and the therapeutic mechanism of Zu' ai Weitai Granule (ZWG) , a TCM preparation. METHODS: The rat model of precancerous lesions of gastric carcinoma was induced by the combined method of N-methyl N' -nitrosoguani-dine (MNNG) and mechanical injury on gastric mucosa. The pathologic morphological changes of gastric mucosa were observed after prophylactic and therapeutic administration of ZWG. In the meantime,the changes in SP, VIP and CGRP contents were determined by immunohistochemical staining. RESULTS: The contents of SP and CGRP in gastric antrum were obviously improved in the ZWG group when compared with those in the control group (P <0. 05). There was no significant difference in VIP content between the two groups (P >0. 05). CONCLUSION: ZWG could improve SP, VIP, and CGRP contents in rats' gastric antrum either as prophylactic administration or therapeutic administration.

Protective effect of astaxanthin on naproxen-induced gastric antral ulceration in rats.

Frequently used for humans as non-steroidal anti-inflammatory drug, naproxen has been known to induce ulcerative gastric lesion. The present study investigated the in vivo protective effect of astaxanthin isolated from Xanthophyllomyces dendrorhous against naproxen-induced gastric antral ulceration in rats. The oral administration of astaxanthin (1, 5, and 25 mg/kg of body weight) showed a significant protection against naproxen (80 mg/kg of body weight)-induced gastric antral ulcer and inhibited elevation of the lipid peroxide level in gastric mucosa. In addition, pretreatment of astaxanthin resulted in a significant increase in the activities of radical scavenging enzymes such as superoxide dismutase, catalase, and glutathione peroxidase. A histologic examination clearly proved that the acute gastric mucosal lesion induced by naproxen nearly disappeared after the pretreatment of astaxanthin. These results suggest that astaxanthin removes the lipid peroxides and free radicals induced by naproxen, and it may offer potential remedy of gastric ulceration.

Essential role of magnesium ion in water for colonization of Helicobacter pylori in 2-week-old miniature pigs.

This study was designed to determine whether magnesium ion in water would influence the colonization of Helicobacter pylori in 2-week-old miniature pigs. Groups A (2 pigs) and B (1 pig) were both fed a milk diet dissolved in drinking water, Group C (2 pigs) was fed a milk diet dissolved in deionized distilled water (DDW), and Group D (1 pig) was fed a milk diet dissolved in DDW supplemented with MgCl2. Groups B, C, and D were all challenged with H. pylori, and Group A was not. Necropsy was performed on the pigs on postinfection Day 5, and biopsy specimens were taken from 16 sites of the stomach. H. pylori were recovered from 11 of 16 sites in Group B, 1 of 32 sites in Group C, and 13 of 16 sites in Group D. On the other hand, the degree of lymphocyte infiltration increased in the order of Group A < Group B < Group C < Group D. These observations suggest that magnesium ion in drinking water is essential for the colonization of H. pylori in the pig stomach. Possible mechanisms for the lymphocyte infiltration are discussed.

Effects of extract F of red-rooted Salvia on mucosal lesions of gastric corpus and antrum induced by hemorrhagic shock-reperfusion in rats.

AIM: To compare the effects of extract F of red-rooted Salvia (EFRRS) on mucosal lesions of gastric corpus and antrum induced by hemorrhagic shock and reperfusion in rats. METHODS: The rats were subject to hemorrhagic shock and followed by reperfusion, and were divided randomly into two groups. Group 1 received saline, and group 2 received EFRRS intravenously. The index of gastric mucosal lesions (IGML) was expressed as the percentage of lesional area in the corpus or antrum. The degree of gastric mucosal lesions (DGML) was catalogued grade 0,1,2 and 3. The concentrations of prostaglandins (PGs) were measured by radioimmunoassay. The concentration of MDA was measured according to the procedures of Asakawa. The activity of SOD was measured by the biochemical way. The growth rates or inhibitory rates of above-mentioned parameters were calculated. RESULTS: As compared with IGML (%), grade 3 damage (%) and MDA content (nmol/g tissue) of gastric antrum which were respectively 7.96 +/- 0.59, 34.86 +/- 4.96 and 156.98 +/- 16.12, those of gastric corpus which were respectively 23.18 +/- 6.82, 58.44 +/- 9.07 and 230.56 +/- 19.37 increased markedly (P <0.01), whereas the grade 0 damage, grade 1 damage, the concentrations of PGE(2) and PGI(2)(pg/mg tissue), the ratio of PGI(2)/TXA(2) and the activity of SOD (U/g tissue) of corpus which were respectively 3.01 +/- 1.01, 8.35 +/- 1.95, 540.48 +/- 182.78, 714.38 +/- 123.74, 17.38 +/- 5.93 and 134.29 +/- 13.35 were markedly lower than those of antrum which were respectively 13.92 +/- 2.25, 26.78 +/- 6.06, 2218.56 +/- 433.12, 2531.76 +/- 492.35, 43.46 +/- 8.51 and 187.45 +/- 17.67 (P<0.01) after hemorrhagic shock and reperfusion. After intravenous EFRRS, the growth rates (%) of grade 0 damage, grade 1 damage, the concentrations of PGE(2) and PGI(2), the ratio of PGI(2)/TXA(2) and the activity of SOD of corpus which were respectively 632.56, 308.62, 40.75, 74.75, 92.29 and 122.25 were higher than those in antrum which were respectively 104.89, 58.40, 11.12, 56.58, 30.65 and 82.64, whereas the inhibitory rates (%) of IGML, grade 3 damage and MDA content of gastric corpus were 82.93, 65.32 and 59.09, being higher than those of gastric antrum which were 76.64, 53.18 and 42.37. CONCLUSION: After hemorrhagic shock reperfusion, the gastric mucosal lesions in the corpus were more severe than those in the antrum, which were related not only to the different distribution of endogenous PGs in the mucosa, but also to the different ability of anti-oxidation of the mucosa. The protective effect of EFRRS on the gastric mucosa in the corpus was more evident than that in the antrum, which was related to higher growth degree of PGs contents and anti-oxitative ability in gastric corpus after administration of EFRRS.

Inhibition of 15-hydroxyprostaglandin dehydrogenase activity in rabbit gastric antral mucosa by panaxynol isolated from oriental medicines.

Panaxynol is a polyacetylene compound with anti-inflammatory and anti-platelet-aggregatory effects isolated from commonly used oriental medicines. The effects of panaxynol on the activity of prostaglandin-synthesizing and catabolizing enzymes in the rabbit gastric antral mucosa have been examined. At concentrations ranging from 25 to 200 microM panaxynol had no effect on the synthesis of prostaglandins E2, F2alpha and D2 from exogenous arachidonic acid in the microsomal fraction of the gastric mucosa whereas at 25-200 microM it dose-dependently inhibited the activity of 15-hydroxyprostaglandin dehydrogenase (PGDH), which catalyses the initial step of prostaglandin catabolism, in the cytosolic fraction. The concentration required for 50% inhibition (IC50) was approximately 25 microM. Inhibition of PGDH by panaxynol was non-competitive with regard to NAD+ and prostaglandin E2. These results suggest that panaxynol has the potential to inhibit PGDH activity in gastric mucosa, possibly as a result of pharmacological activity.