Refractory GERD, beyond proton pump inhibitors.

Pharmacologic therapy, surgery, minimally invasive therapies, and alternative therapies are different options available for the management of refractory GERD. The choice may depend on the cause of refractoriness. Increased gastric acid suppression therapy might be useful in the rare patients with persistent elevated esophageal acid exposure on proton pump inhibitors (PPI). Potassium-competitive acid blockers (P-CAB) might induce a more important acid inhibition than PPI. Baclofen might act as a reflux inhibitor and demonstrates a significant efficacy in rumination syndrome. The role of topical antacid-alginate in refractory GERD might be limited. Surgery might be a valid option in case of persistent pathological acid esophageal exposure despite PPI. Further evaluation of minimally invasive procedures is necessary. Finally diet, diaphragmatic breathing and transcutaneous electrical acustimulation might be of interest in patients with esophageal hypersensivity or functional symptoms.

Pediatric Collagenous Gastritis and Colitis: A Case Series and Review of the Literature.

INTRODUCTION: Collagenous gastritis is a rare disease characterized by the subepithelial deposition of collagen bands. Two phenotypes of the disease have been described: a pediatric-onset and an adult-onset type. The adult-onset form is associated with collagenous colitis and autoimmune disorders. No effective treatment has been identified to date. OBJECTIVE: We aim to describe the clinical features and outcomes of patients in our cohort and provide a summary of published pediatric cases with collagenous gastritis and colitis reported to date to gather information that will contribute to improved knowledge of this rare condition. METHODS: A retrospective chart review of all patients with collagenous gastritis and/or colitis who were treated at the Royal Children's Hospital, Melbourne, was performed. A literature review was also conducted. RESULTS: A total of 12 cases of collagenous gastritis were reviewed. Three of 12 (25%) patients had associated collagenous colitis. The most common clinical presentation was iron deficiency anemia. Nine (75%) patients were followed up, and repeat endoscopies were performed in 8 (67%). Iron deficiency anemia resolved in all patients on oral iron supplementation. Histologic improvement was only identified in one patient with the adult phenotype who had been treated with oral corticosteroids and azathioprine. CONCLUSIONS: Collagenous gastritis is a rare condition in children. A small proportion of children develop features of the "'adult" phenotype at a very young age. Patients with collagenous gastritis require long-term follow-up and monitoring of their disease. Further randomized clinical trials are needed to establish an effective therapeutic strategy.

Gastric Mucosal Oxidative Stress Markers in Children with Helicobacter Pylori Infection.

BACKGROUND: 'Helicobacter pylori' "H. pylori" is one of the most common infections that colonizes human gastric mucosa and generates reactive oxygen and nitrogen species. The aim of this study was to evaluate the oxidative stress markers in the gastric mucosa of "H. pylori"- infected children. PATIENTS AND METHODS: The present study was carried out on 60 children infected with "H. pylori" including 28 males, 32 females with their age ranging from 7-10 years and mean age value of 8.5 ± 1.65 years (Group I). This study included also 60 healthy children as a control group including 26 males and 34 females with their age ranging from 7-11 years and mean age value of 8.99 ± 1.63 years (Group II). All children were subjected to full history taking, thorough clinical examination, diagnosis of "H. pylori" infection through "H. pylori" stool antigen testing using enzyme immunoassay kit (Group I and II) and gastric antrum mucosal biopsies which were tested for urease activity using Campylobacter like organism test (CLO test) (Group I only) and measurement of gastric mucosal oxidative stress markers including Malondialdehyde (MDA), Superoxide dismutase (SOD), reduced glutathione (GSH), Catalase and nitric oxide (NO) [The sum of Nitrite (NO2 -) and Nitrate (NO3 -)]. RESULTS: The main clinical presentations in studied patients and controls were recurrent abdominal pain, recurrent vomiting, dyspepsia and hematemesis with no significant difference between patients and controls as regard abdominal pain, vomiting or dyspepsia but hematemesis was found only in patients. There were significant differences between patients and controls as regard site and duration of abdominal pain with epigastrium being the most common site of pain in patients versus diffuse abdominal pain in control group with significantly longer duration of abdominal pain in patients compared with controls. "H. pylori" infected children has significantly lower gastric mucosal nitric oxide and reduced glutathione and significantly higher gastric mucosal MDA, catalase and SOD compared to controls (nitric oxide was 85.68 ± 23.16 nmol/gm in patients versus 106.423±2.111 nmol/gm in controls, reduced glutathione in patients was 1.83 ± 0.16 nmol/gm versus 2.44 ± 0.07 nmol/gm in controls, MDA in patients was 189.15 ± 6.14 nmol/gm versus 166.21 ± 3.13 nmol/gm in controls, catalase was 57.38 ± 19.85 unit/gm in patients versus 36.51 ± 2.34 unit/gm in controls and SOD in patients was 375.52 ± 26.51 unit/gm versus 318.51 ± 32.06 unit/gm in controls. CONCLUSION: "H. pylori" infection is associated with gastric mucosal oxidative stress with significantly lower gastric mucosal nitric oxide and reduced glutathione and significantly higher gastric mucosal MDA, Catalase and SOD in patients compared to controls. RECOMMENDATIONS: Antioxidants may be an important adjuvant therapy for "H. pylori" infection as this infection is associated with gastric mucosal oxidative stress.

Animal models of chemotherapy-induced mucositis: translational relevance and challenges.

Chemotherapy for cancer patients induces damaging tissue reactions along the epithelium of the gastrointestinal tract (GIT). This chemotherapy-induced mucositis (CIM) is a serious side effect of cytotoxic drugs, and several animal models of CIM have been developed, mainly in rodents and piglets, to help understand the progression of CIM and how to prevent it. Animal models allow highly controlled experimental conditions, detailed organ (e.g., GIT) insights, standardized, clinically relevant treatment regimens, and discovery of new biomarkers. Still, surprisingly few results from animal models have been translated into clinical CIM management and treatments. The results obtained from specific animal models can be difficult to translate to the diverse range of CIM manifestations in patients, which vary according to the antineoplastic drugs, dose, underlying (cancer) disease, and patient characteristics (e.g., age, genetics, and body constitution). Another factor that hinders the direct use of results from animals is inadequate collaboration between basic science and clinical science in relation to CIM. Here, we briefly describe CIM pathophysiology, particularly the basic knowledge that has been obtained from CIM animal models. These model studies have indicated potential new preventive and ameliorating interventions, including supplementation with natural bioactive diets (e.g., milk fractions, colostrum, and plant extracts), nutrients (e.g., polyunsaturated fatty acids, short-chain fatty acids, and glutamine), and growth factor peptides (e.g., transforming growth factor and glucagon-like peptide-2), as well as manipulations of the gut microbiota (e.g., prebiotics, probiotics, and antibiotics). Rodent CIM models allow well-controlled, in-depth studies of animals with or without tumors while pig models more easily make clinically relevant treatment regimens possible. In synergy, animal models of CIM provide the basic physiological understanding and the new ideas for treatment that are required to make competent decisions in clinical practice.

[Effects of Xiangsha Liujunzi decoction on TLR signal pathway in gastric mucosa tissues of rats with Helicobacter pylori-induced chronic atrophic gastritis].

To explore the effects and mechanism of Xiangsha Liujunzi decoction on TLR signal pathway in gastric mucosa tissues of rats with Helicobacter pylori-related gastritis, sixty SD rats were randomly divided into control group, model group, high concentration of Xiangsha Liujunzi decoction group, moderate concentration of Xiangsha Liujunzi decoction group, low concentrations of Xiangsha Liujunzi decoction group and SB203580-treated group, with 10 rats in each group. SD rats of Hp-associated chronic atrophic gastritis models were established by intragastric gavage of Helicobacter pylori (HP) suspension. Changes in the gastric mucosa of rats were assessed by histopathology. ELISA was applied to detect the expressions of TNF-α and IL-6 in the serum, and the activity of iNOS in gastric mucosa. The content of NO in the gastric mucosa was tested by nitrate reductive enzymatic. The expressions of TLR2, TLR4, P38MAPK, NF-κB were detected by QPCR and Western-blot. The results indicated that the clinical symptoms of rats and pathological changes of gastric mucosa were improved in Xiangsha Liujunzi decoction group. Compared with normal control group, the protein expressions of TLR2, TLR4, p-P38MAPK and NF-κB in gastric mucosa of model group rats increased (P<0.01) with the levels of TNF-α and IL-6 in the serum, and the activity of iNOS and the content of NO in gastric mucosa increased. Compared with model group, the expressions decreased in Xiangsha Liujunzi decoction group, especially in the high concentration of Xiangsha Liujunzi decoction group(P<0.01), with gradually increased rate of HP eradication and decreased pathological grades of chronic atrophic gastritis. The serum level of TNF-α and IL-6 decreased from (24.313±2.261) µg•L ⁻¹ to (15.195±1.235) µg•L-1(P<0.01) and from (77.416±8.095) µg•L ⁻¹ to (33.150±2.532) µg•L ⁻¹ (P<0.01), and the activity of iNOS and the content of NO in gastric mucosa decreased from (1.530±0.206) U•mg ⁻¹ to (0.802±0.091) U•mg ⁻¹ (P<0.01) and from (0.907±0.032) mmol•g ⁻¹ to (0.335±0.026) mmol•g ⁻¹ (P<0.01) after the treatment of high concentration of Xiangsha Liujunzi decoction. All the effects increased with the increasing dosage of Xiangsha Liujunzi decoction from 0.324 g•mg ⁻¹ to 1.296 g•mg ⁻¹. The protein expressions of NF-κB decreased in the gastric mucosa after treated with P38MAPK specific inhibitor-SB203580. In the rats model, HP infection results in chronic atrophic gastritis through the activation of TLR2, TLR4/MAPK/NF-κB/iNOS/NO signal pathway. Xiangsha Liujunzi decoction can eradicate H. pylori and alleviate chronic atrophic gastric mucosal inflammation. The treatment is effective and safe to cure HP-induced chronic atrophic gastritis.

Biochanin a gastroprotective effects in ethanol-induced gastric mucosal ulceration in rats.

BACKGROUND: Biochanin A notable bioactive compound which is found in so many traditional medicinal plant. In vivo study was conducted to assess the protective effect of biochanin A on the gastric wall of Spraguedawley rats` stomachs. METHODOLOGY: The experimental set included different animal groups. Specifically, four groups with gastric mucosal lesions were receiving either a) Ulcer control group treated with absolute ethanol (5 ml/kg), b) 20 mg/kg of omeprazole as reference group, c) 25 of biochanin A, d) 50 mg/kg of biochanin A. Histopathological sectioning followed by immunohistochemistry staining were undertaken to evaluate the influence of the different treatments on gastric wall mucosal layer. The gastric secretions were collected in the form of homogenate and exposed to superoxide dismutase (SOD) and nitric oxide enzyme (NO) and the level of malondialdehyde (MDA) and protein content were measured. Ulceration and patchy haemorrhage were clearly observed by light microscopy. The morphology of the gastric wall as confirmed by immunohistochemistry and fluorescent microscopic observations, exhibited sever deformity with notable thickness, oedematous and complete loss of the mucosal coverage however the biochanin-pretreated animals, similar to the omeprazole-pretreated animals, showed less damage compared to the ulcer control group. Moreover, up-regulation of Hsp70 protein and down-regulation of Bax protein were detected in the biochanin A pre-treated groups and the gastric glandular mucosa was positively stained with Periodic Acid Schiff (PAS) staining and the Leucocytes infiltration was commonly seen. Biochanin A displayed a great increase in SOD and NO levels and decreased the release of MDA. CONCLUSIONS: This gastroprotective effect of biochanin A could be attributed to the enhancement of cellular metabolic cycles perceived as an increase in the SOD, NO activity, and decrease in the level of MDA, and also decrease in level of Bax expression and increase the Hsp70 expression level.

Gastroprotective effect and mechanism of patchouli alcohol against ethanol, indomethacin and stress-induced ulcer in rats.

Pogostemonis Herba is an important Chinese medicine widely used in the treatment of gastrointestinal dysfunction. Patchouli alcohol (PA), a tricyclic sesquiterpene, is the major active constituent of Pogostemonis Herba. This study aimed to investigate the possible anti-ulcerogenic potential of PA and the underlying mechanism against ethanol, indomethacin and water immersion restraint-induced gastric ulcers in rats. Gross and histological gastric lesions, biochemical and immunological parameters were taken into consideration. The gastric mucus content and the antisecretory activity were analyzed through pylorus ligature model in rats. Results indicated that oral administration with PA significantly reduced the ulcer areas induced by ethanol, indomethacin and water immersion restraint. PA pretreatment significantly promoted gastric prostaglandin E2 (PGE2) and non-protein sulfhydryl group (NP-SH) levels, upregulated the cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) mRNA expression, and considerably boosted the gastric blood flow (GBF) and gastric mucus production in comparison with vehicle. In addition, PA modulated the levels of interleukin-6 (IL-6), interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α). The levels of glutathione (GSH), catalase (CAT) and malonaldehyde (MDA) were also restored by PA. However, the gastric secretion parameters (pH, volume of gastric juice and pepsin) did not show any significant alteration. These findings suggest that PA exhibited significant gastroprotective effects against gastric ulceration. The underlying mechanisms might involve the stimulation of COX-mediated PGE2, improvement of antioxidant and anti-inflammatory status, preservation of GBF and NP-SH, as well as boost of gastric mucus production.

[The effect of low-level laser therapy on gastric mucosa microcirculation in patients with gastroesophageal reflux disease].

OBJECTIVE: To study the influence of laser radiation on the parameters of microcirculation in patients with gastroesophageal reflux disease (GERD). MATERIALS AND METHODS: The examined 112 patients with GERD aged 19 to 79 years. 78 patients were given a ten-day course of intravenous laser therapy, which was conducted with the help of the apparatus of laser therapy "matrix-vlok" (produced by "the matrix", Russia) with wavelength 0,405 microns, the radiation power at the output of the main fiber 1-1,5 mW, continuous mode radiation. The studied parameters were determined before and after treatment. RESULTS: The obtained data testify to the improvement of microcirculation in patients with GERD under the influence of laser therapy.

Gastric electrical stimulation for abdominal pain in patients with symptoms of gastroparesis.

Abdominal pain physiology may be better understood studying electrophysiology, histology, and symptom scores in patients with the symptoms of gastroparesis (Gp) treated with gastric electrical stimulation (GES). Ninety-five Gp patients' symptoms were recorded at baseline and during temporary and permanent GES. Gastric-emptying times and cutaneous, mucosal, and serosal electrogastrograms were obtained. S100-stained, full-thickness gastric biopsies were compared with autopsy controls. Sixty-eight patients reported severe pain at baseline. Severe pain patients' mean pain scores decreased with temporary GES from 3.62 to 1.29 (P < 0.001) and nonsevere pain from 1.26 to 0.67 (P = 0.01). With permanent GES, severe mean pain scores fell to 2.30 (P < 0.001); nonsevere pain changed to 1.60 (P = 0.221). Mean follow-up was 275 days. Mean cutaneous, mucosal, and serosal frequencies and frequency-to-amplitude ratios were markedly higher than literature controls. For patients with Gp overall and subdivided by etiology and severity of pain, S-100 neuronal fibers were significantly reduced in both muscularis propria layers. GES improved severe pain associated with symptoms of Gp. This severe pain is associated with abnormal electrogastrographic activity and loss of S100 neuronal fibers in the stomach's inner and outer muscularis propria and, therefore, could be the result of gastric neuropathy.

Food intake and body weight responses to intermittent vs. continuous gastric electrical stimulation in diet-induced obese rats.

BACKGROUND: Gastric electrical stimulation (GES) has recently been introduced as a potential therapy for the treatment of obesity. The main challenge for the new generation of devices is to achieve desired clinical outcomes at a suitably low level of energy consumption. The aim of this study is to compare the effectiveness of GES with continuous and intermittent duty cycles in reducing food intake and body weight in diet-induced obesity-prone rats. METHODS: In macro duty cycle experiment, 40 rats were divided into groups to receive a sham GES, continuous GES, or intermittent GES (15 min On-45 min Off or 15 min On-15 min Off) for 28 days. In micro duty cycle experiment, 18 rats received cross-over treatment of continuous stimulation, 60 % time cycle or 40 % time cycle. Food intake, body weight, gastric emptying and ghrelin level were measured to evaluate the effect of different GES. RESULTS: GES with macro duty cycle intensity-dependently reduced mean daily food intake increase by 18.6, 10.2 and -6.0 % compared to 42.7 % with sham GES and body weight gain by 6.1 %, 3.4 and -0.8 % compared to 5 % with sham GES. Daily food intake decreased with increasing micro duty cycle intensity, averaging 16.5, 15.6 and 13.7 g/day under 40 % cycle, 60 % cycle and continuous stimulation respectively. Gastric emptying was intensity-dependently delayed by GES. GES has no effect in modulating plasma ghrelin level. CONCLUSIONS: GES energy-dependently reduces food intake, body weight and gastric emptying. Peripheral modulation of plasma ghrelin level is not related to the GES effects.

[Gastroprotective action of the nettle extract in experimental peptic ulcer].

Nettle extract produced from leaves crushed to 40-70 nm fragments protects the stomach mucous membrane, and does it better than the extract derived from same leaves crushed to 1 mm fragments, on the models of peptic ulcers caused by acetylsalicylic acid, histamine, prednisolone, and immobilized stress. The antiulcer activity of the nettle extract from 40-70 nm fragments is comparable with the effect of buckthorn oil. Nettle extracts also hinder the excess acid secretion and diminish the acidity of stomach juice in experimental peptic ulcer caused by pylorus ligation.

Design, synthesis and pharmacological evaluation of novel azole derivatives of aryl acetic acid as anti-inflammatory and analgesic agents.

A series of substituted azole derivatives (3a-e, 4a-e and 5a-e) were synthesised by the cyclisation of N(1)(diphenylethanoyl)-N(4)-substituted phenyl thiosemicarbazides under various reaction conditions. These compounds were tested in vivo for their anti-inflammatory activity. The compounds which showed activity comparable to the standard drug ibuprofen, were screened for their analgesic, ulcerogenic and lipid peroxidation activities. The compounds 5-(diphenylmethyl)-N-(4-fluorophenyl)-1,3,4-oxadiazol-2-amine (3b) and 5-(diphenylmethyl)-N-(3-chloro-4-fluorophenyl)-1,3,4-oxadiazol-2-amine (3c) emerged as the most active compounds of the series, and were moderately more potent than the standard drug, ibuprofen. (This abstract was published in Inflammation Research, Supplement 2, Volume 56, page A101, 2008.).

Mucosal strengthening activity of central and peripheral melatonin in the mechanism of gastric defense.

This review summarizes the involvement of centrally and peripherally applied melatonin, a major hormone of pineal gland, in the mechanism of gastric mucosal integrity, gastroprotection and ulcer healing. Melatonin was originally shown to attenuate gastric mucosal lesions but the controversy exists in the literature as to whether melatonin derived from the pineal gland, considered as the major source of this indole or rather that locally generated from L-tryptophan within gastric mucosa, plays predominant role in the mechanism of gastrointestinal integrity. Both, intragastric (i.g.) and intracerebroventricular (i.c.v.) administration of melatonin and its precursor, L-tryptophan to rats without or with removed pineal gland by pinealectomy attenuates in the dose-dependent manner the formation of on gastric lesions induced by topical irritants and water immersion restraint stress (WRS). Melatonin accelerated the gastric ulcer healing and this was accompanied by the rise in gastric blood flow (GBF), the plasma melatonin and gastrin levels, the mucosal generation of PGE(2) and luminal NO content. Pinealectomy, which suppresses the plasma melatonin levels, markedly aggravated the gastric lesions induced by WRS. Concurrent supplementation of pinealectomized animals with melatonin or L-tryptophan, the melatonin precursor, attenuated the lesions induced by WRS. Treatment with luzindole, an antagonist of Mel(2) receptors, or with L-NNA, the NO-synthase inhibitor, significantly attenuated melatonin- and L-tryptophan-induced protection and the acceleration of ulcer healing and the accompanying increase in the GBF and luminal content of NO. We conclude that 1) exogenous melatonin and that released from the L-tryptophan attenuate lesions induced by topical irritant such as ethanol and WRS via interaction with MT(2) receptors and due to an enhancement of gastric microcirculation, probably mediated by NO and PG derived from cNOS, iNOS and COX-2 overexpression and activity, and 2) the pineal gland plays an important role in the limitation of WRS-induced gastric lesions and acceleration of ulcer healing via releasing melatonin predominately at night time, that exerts gastroprotective and ulcer healing actions.

Clinical effects of the method for warming the middle-jiao and strengthening the spleen on gastric mucosa repair in chronic gastritis patients.

OBJECTIVE: To observe clinical effects of the method for warming the middle-jiao and strengthening the spleen on gastric mucosa repair in chronic gastritis patients. METHODS: The 42 cases of the treatment group were orally adiministered Yiweikang Capsule; while the other 25 cases in the control group were orally given Wenweishu Capsule. Both the groups were observed for 2 months. RESULTS: The total effective rate in the treatment group was obviously higher than that of the control group (P < 0.05), with statistical significance shown by the TCM symptom score, gastroscopic examination and the HP test (P < 0.05 or P < 0.01). CONCLUSIONS: Yiweikang Capsule is an effective medicine for chronic gastritis.

Healing property of the Piper betel phenol, allylpyrocatechol against indomethacin-induced stomach ulceration and mechanism of action.

AIM: To evaluate the protective activity of allylpyrocatechol (APC), the major antioxidant constituent of Piper betel, against the indomethacin-induced stomach ulceration in the rat model and correlates with its antioxidative and mucin protecting properties. METHODS: Male Sprague-Dawley rats were divided into five groups. Normal control rats (group I) were given the vehicle oral dose of gum acacia in distilled water (1 mL per rat); ulcerated control and treated rats (groups II-V) were given a single dose of indomethacin (30 mg/kg body wt.); group II rats were sacrificed 4 h after indomethacin administration; groups III-V rats were given the vehicle (1 mL per rat) or APC (2 mg/kg body wt.) or misoprostol (1.43 mug/kg body wt.) once daily by oral intubation for 7 d starting from 4 h after the indomethacin administration. After 7 d, the stomach tissues were excised for histological examination and biochemical analysis. RESULTS: Treatment with APC (2 mg/kg body wt per day) and misoprostol (1.43 mug/kg body wt per day) for 7 d could effectively heal the stomach ulceration as revealed from the ulcer index and histopathological studies. Compared to the zero day ulcerated group, treatment with APC and misoprostol reduced the ulcer index by 93.4% and 85.4% respectively (P < 0.05). Both APC and misoprostol accelerated ulcer healing observed in natural recovery (P < 0.05), their respective healing capacities not being significantly different. The healing capacities of APC and misoprostol could be attributed to their antioxidant activity as well as the ability to enhance the mucin content of the gastric tissues. Compared to the ulcerated untreated rats, those treated with APC and misoprostol showed near normal MDA levels, while the protein levels were 86% and 78% of the normal value respectively (P < 0.05). Likewise, both APC and misoprostol increased the SOD, catalase, and mucin levels significantly (P < 0.05), the effect of APC being better. CONCLUSION: APC can protect indomethacin-induced gastric ulceration due to its antioxidative and mucin protecting properties.

[Expressions of epidermal growth factor receptor signaling substances in gastric mucosal cells influenced by serum derived from rats treated with electroacupuncture at stomach meridian acupoints].

OBJECTIVE: To study the effects of serum derived from rats treated with electroacupuncture at stomach meridian acupoints on the expressions of epidermal growth factor receptor (EGFR) signaling substances phospholipase C gamma-1 (PLC gamma-1), protein kinase C (PKC) and c-myc in gastric mucosal cells. METHODS: Sixty rats were randomly divided into normal group, stomach meridian group, gallbladder meridian group, stomach meridian plus PD153035 group and gallbladder meridian plus PD153035 group. Water-immersion and restrained stress methods were adopted for inducing gastric mucosal injury in the rats. Gastric mucosal cells were separated by using pronase digestion method, and incubated by PD153035, a EGFR inhibitor, and 100 ml/L serum. The expression of PLC gamma-1 in the gastric mucosal cells was tested by enzyme linked-immunosorbent assay (ELISA), while the expression of PKC by isotope incorporate assay and the expression of c-myc by reverse transcription polymerase chain reaction assay (RT-PCR). RESULTS: In gastric mucosal cells, weak expressions of PLC gamma-1, PKC and c-myc were seen in the normal group, and relatively strong expressions of PLC gamma-1, PKC and c-myc were seen in the stomach meridian group and the gallbladder meridian group, among which, the expressions of PLC gamma-1, PKC and c-myc in the stomach meridian group were the strongest, and there was a significant difference between the stomach meridian group and the gallbladder meridian group (P<0.01). Relative weak expressions of PLC gamma-1, PKC and c-myc were seen in the stomach meridian plus PD153035 group and the gallbladder meridian plus PD153035 group, and there was a significant difference between the stomach meridian group and the stomach meridian plus PD153035 group (P<0.01). CONCLUSIONS: The serum derived from the rats treated with electroacupuncture at stomach meridian acupoints can activate the EGFR singling pathway, and this provides an evidence for the theory of "relative particularity between meridians and viscera" in traditional Chinese medicine.

Effect of pre-moxibustion on apoptosis and proliferation of gastric mucosa cells.

AIM: To observe the effects of pre-moxibustion on apoptosis and proliferation of gastric mucosal cell in rats with stress-induced ulcer, and to analyze the relationship between those effects and the expression of heat-shock protein 70 (HSP70). METHODS: Sixty healthy Sprague Dawley rats were randomly assigned into four groups, namely group A, B, C and D. The animal model of stress ulcer was established by water immersion and restraint stress. The rats in group A, B, and D served as the restraint, model, and non-acupoint controls, respectively, while those in group C received moxibustion at Zusanli and Liangmen points. Immunohistochemical methodology was used to detect the expression of HSP70, apoptosis index (AI, multiply 10(-6)/microm(2)) and proliferation index (PCNA-LI, multiply 10(-6)/microm(2)). The mucosal expression of transforming growth factor alpha(TGF-alpha) was detected by radioimmunoassay. RESULTS: Moxibustion at Zusanli and Liangmen points significantly decreased the gastric injury and the apoptosis of gastric mucosal cells, while markedly increased the mucosal expression of TGF-alpha and HSP70 as well as the proliferation of gastric mucosal cells. Compared with group A, ulcer index (UI) (26.8 +/- 9.8 vs 12.0 +/- 5.9, P < 0.01), AI (9.6 +/- 4.2 vs 4.4 +/- 2.6, P < 0.05) and expression of HSP70 (9.6 +/- 4.2 vs 4.4 +/- 2.6, P < 0.05) were significantly increased, but the content of TGF-alpha (104.7 +/- 51.2 pg/mL vs 254.0 +/- 86.9 pg/mL, P < 0.01) and PCNA-LI (6.9 +/- 4.7 vs 14.9 +/- 4.6, P < 0.05) were significantly decreased in group B. However, ulcer index values (UI) and AI were obviously lower in group C compared to groups B and D (14.1 +/- 5.4 vs 26.8 +/- 9.8 and 26.2 +/- 7.7, P < 0.01; 3.0 +/- 1.6 vs 9.6 +/- 4.2 and 8.2 +/- 5.2, P < 0.05, respectively), but content of TGF-alpha (237.0 +/- 72.6 pg/mL vs 104.7 +/- 51.2 pg/mL and 154.1 +/- 61.3 pg/mL, P < 0.01) and expression of HSP70 (0.13 +/- 0.03 vs 0.08 +/- 0.06 and 0.06 +/- 0.04, P < 0.05) were higher in group C. Furthermore, the PCNA-LI was significantly higher in group C than in group B (21.6 +/- 4.1 vs 6.9 +/- 4.7, P < 0.01). CONCLUSION: Moxibustion at Zusanli and Liangmen points has a protective effect on rats gastric mucosa in stress-induced gastric ulcer, which is closely related to its actions in promoting synthesis of TGF-alpha and proliferation of gastric mucosal cells, suppressing gastric mucosal cell apoptosis, and up-regulating HSP70 expression.

Constituents and antiulcer effect of Alchornea glandulosa: activation of cell proliferation in gastric mucosa during the healing process.

Alchornea glandulosa (Euphorbiaceae) is a plant used in folk medicine as an antiulcer agent. Rats pretreated with methanolic extract obtained from the leaves of A. glandulosa (AG) showed a dose-dependent effect and significant reduction of gastric ulcers induced by absolute ethanol at the doses of 500 (57%) and 1000 mg/kg (85%) in relation to the control group. Pretreatment of mice with AG (500, 1000 mg/kg, p.o.) showed dose-dependent activity and significantly decreased the severity of lesions caused by HCl/ethanol and by non steroidal anti inflammatory drug-induced gastric lesions. Pretreatment with AG also induced antisecretory action via local and systemic routes and a significant decrease in the total gastric acid content. The gastroprotective effects of AG involved the participation of nitric oxide and increased levels of endogenous sulfhydryl compounds, which are defensive mechanisms of the gastrointestinal mucosa against aggressive factors. The ability of AG to heal gastric ulcers was evaluated after 14 consecutive days of treatment. The results showed that single oral administrations of AG (250 mg/kg/once daily) potently stimulates gastric epithelial cell proliferation that contributes to the accelerated healing of gastric ulcers induced by acetic acid. In addition, no subacute toxicity (body weight gain, vital organs, and serum biochemical parameters) was observed during treatment with AG. Phytochemical investigation of AG led to the isolation of myricetin-3-O-alpha-L-rhamnopyranoside, quercetin-3-O-alpha-L-arabinopyranoside, quercetin-3-O-beta-D-galactopyranoside, quercetin, amentoflavone, methyl gallate, gallic acid, and pterogynidine. We also established the phytochemical profile of AG with the quantification of total phenolic compounds. These compounds may contribute to the observed antiulcerogenic effects of AG.

Effect of shenfu injection on gastrointestinal microcirculation in rabbits after myocardial ischemia-reperfusion injury.

AIM: To investigate the effect of shenfu injection on gastrointestinal microcirculation after myocardial ischemic-reperfusion (IR) injury in rabbits and probe into the mechanism. METHODS: Forty healthy flap-eared white rabbits were randomly divided into 4 groups: IR injury control group (group I), shenfu injection 5 mL/kg per h group (group II), shenfu injection 10 mL/kg per h group (group III) and shenfu injection 20 mL/kg per h group (group IV). The four groups were treated with Lactated Ringer's solution, shenfu injection 5, 10, and 20 mL/ kg per h were infused intravenously 30 min before experiment respectively. The values of hemodynamics [mean arterial pressure (MAP), heart rate (HR), gastric intramucosal partial pressure of carbon dioxide (PCO2), blood gas analysis and pH] were measured and compared with those before myocardial ischemia, 60 min after myocardial ischemia and 60, 90, and 180 min after reperfusion. RESULTS: The MAP, HR and gastric intramucosal pH were (70.50 +/- 4.50) kPa, (165 +/- 14) beats per min, 7.032 +/- 0.024 in group I 60 min after myocardial ischemia, which were significantly decreased compared with those before myocardial ischemia (88.50 +/- 9.75 kPa, 217 +/- 18 beats per min, 7.112 +/- 0.035, P < 0.05). The MAP, HR and gastric intramucosal pH were significantly decreased in group I 60, 90, and 180 min after reperfusion (61.50 +/- 5.25 kPa, 133 +/- 31 beats per min, 6.997 +/- 0.025) compared with those before reperfusion respectively (P < 0.05), whereas the values were insignificantly different in groups II, III or IV after reperfusion, compared with those before reperfusion, and there were no significant differences between groups II, III, and IV after reperfusion. CONCLUSION: Pre-infusion of shenfu injection has a protective effect on gastrointestinal microcirculation after myocardial IR injury in rabbits, in a dose independent manner.