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Intragastric injection of botulinum toxin for the treatment of obesity. Where are we?

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World Journal of Gastroenterology 2008年第12期14卷 1805-1809页

作者： Diego Garcia-Compean Hector Maldonado Garza Department of Gastroenterology Faculty of Medicine University Hospital. Ave Madero y Gonzalitos Col Mitras Centro Monterrey 64700 Mexico

Obesity has reached epidemic proportions particularly in western countries. Most non-surgical treatments of this condition are disappointing. Since 2005, several studies evaluating the effect of Botulinum Toxin type A (BT-A) in gastric antrum by means of endoscopy for the treatment of obesity have been published. This treatment modality was based on the observation that gastric injection of BT-A in laparatomized rats induced a significant reduction of food intake and body weight. Nowadays, 6 studies have been published yielding conflicting results. Differences in selection of patients, doses of BT-A, method of administration of the toxin and instruments of evaluation of some parameters among these studies may be the cause of divergent results. We discuss herein some important features of these studies pointing out on differences among them. At the same time, based on the knowledge of physiological characteristics of normal and abnormal gastric function related with feeding, we discuss the probable causes of failure observed in these trials. Finally, we give some guidelines concerning the way that future research in this field may follow, not without calling attention to disadvantages of this treatment.

关键词： Botulinum toxin Obesity gastric emptying gastric motility Gastroparesis

gastric electrical stimulation for gastroparesis:A goal greatly pursued,but not yet attained

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World Journal of Gastroenterology 2011年第3期17卷 273-282页

作者： Mauro Bortolotti Department of Internal Medicine and Gastroenterology University of Bologna

The lack of an effective medical treatment for gastroparesis has pushed the research of new techniques of gastric electrical stimulation (GES) for nearly half a century of experimentation with a large variety of electrical stimuli delivered to the gastric wall of animals and patients with gastroparesis. Three principal methods are currently available: gastric low-frequency/high-energy GES with long pulse stimulation, high-frequency/low-energy GES with short pulse stimulation and neural sequential GES. The first method aims to reset a regular slow wave rhythm, but has variable effects on contractions and requires devices with large and heavy batteries unsuitable for implantation. High-frequency/low-energy GES, although inadequate to restore a normal gastric electro-mechanical activity, improves dyspeptic symptoms, such as nausea and vomiting, giving patients a better quality of life together with a more satisfactory nutritional status and is suitable for implantation. Unfortunately, the numerous clinical studies using this type of GES, with the exception of two, were not controlled and there is a need for definitive verification of the effectiveness of this technique to justify the cost and the risks of this procedure. The last method, which is neural sequential GES, consists of a microprocessor-controlled sequential activation of a series of annular electrodes along the distal two thirds of the stomach and is able to induce propagated contractions causing forceful emptying of the gastric content. The latter method is the most promising, but has been used only in animals and needs to be tested in patients with gastroparesis before it is regarded as a solution for this disease.

关键词： gastric electrical stimulation gastric emptying gastric motility gastric myoelectric activity Gastroparesis Prokinetic drugs

Dendroaspis natriuretic peptide relaxes gastric antral circular smooth muscle of guinea-pig through thecGMP/cGMP-dependent protein kinase pathway

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World Journal of Gastroenterology 2008年第35期14卷 5461-5466页

作者： Chun-Yu Cai Zheng-Xu Cai Xin-Yi Gu Lu-Juan Shan Yong-Xiao Wang Xue-Zhe Yin Qing-Hui Qi Hui-Shu Guo Department of Internal Medicine the Affiliated Hospital of Yanbian University Yanji 133000 Jilin Province China Department of Neurology the First Affiliated Hospital of Dalian Medical University Dalian 116011 Liaoning Province China Centralab Zhongshan Affiliated Hospital of Dalian University Dalian 116001 Liaoning Province China Centralab the First Affiliated Hospital of Dalian Medical University Dalian 116011 Liaoning Province China Center for Cardiovascular Sciences Albany Medical College Albany NY 12208 United States

AIM: To systematically investigate if cGMP/cGMP- dependent protein kinase G (PKG) signaling pathway may participate in dendroaspis natriuretic peptide (DNP)-induced relaxation of gastric circular smooth muscle. METHODS: The content of cGMP in guinea pig gastric antral smooth muscle tissue and perfusion solution were measured using radioimmunoassay; spontaneous contraction of gastric antral circular muscles recorded using a 4-channel physiograph; and Ca2+-activated K+ currents (IK(Ca)) and spontaneous transient outward currents (STOCs) in isolated gastric antral myocytes were recorded using the whole-cell patch clamp technique. RESULTS: DNP markedly enhanced cGMP levels in gastric antral smooth muscle tissue and in the perfusion medium. DNP induced relaxation in gastricantral circular smooth muscle, which was inhibited by KT5823, a cGMP-dependent PKG inhibitor. DNP increased IK(Ca). This effect was almost completely blocked by KT5823, and partially blocked by LY83583, an inhibitor of guanylate cyclase to change the production of cGMP. DNP also increased STOCs. The effect of DNP on STOCs was abolished in the presence of KT5823, but not affected by KT-5720, a PKA-specific inhibitor. CONCLUSION: DNP activates IK(Ca) and relaxes guinea-pig gastric antral circular smooth muscle via the cGMP/PKG-dependent singling axis instead of cAMP/ PKA pathway.

关键词： Dendroaspis natriuretic peptide Cyclic guanosine monophosphate Protein kinase G Proteinkinase A gastric motility

Investigation of fundo-antral reflex in human beings

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World Journal of Gastroenterology 2005年第42期11卷 6676-6680页

作者： Satish SC Rao Anjana Kumar Brent Harris Bruce Brown Konrad S Schulze Department of Internal Medicine University of Iowa Carver College of Medicine Iowa City Iowa United States

AIM： To examine the sensory and motor response（s） of the stomach following fundic distention and to assess whether cholinergic mechanisms influence these responses. METHODS： Fundic tone, gastric sensory responses and antral motility were evaluated in eight healthy volunteers after a probe with two sensors was placed in the antrum and a highly compliant balloon in the fundus. Isobaric balloon distentions were performed with a barostat. Study was repeated in six volunteers after intravenous atropine was given. RESULTS： Fundic antral contractions curve was higher First sensation distention induced large amplitude in all subjects. The area under the （P〈0.05） during fundic distention. was reported at 12±4 mmHg, moderate sensation at 18±4 mmHg and discomfort at 21±4 mmHg. Discomfort was associated with a decrease in antral motility. After atropine was given, the area under the curve of pressure waves and fundic tone decreased （P〈0.05）. Sensory thresholds were not affected. CONCLUSIONS： Fundic balloon distention induces an antral motor response, the fundo-antral reflex, which in part may be mediated by cholinergic mechanisms.

关键词： gastric motility Reflex Fundo-antral reflex Sensation

Mechanisms underlying feed intolerance in the critically ill: Implications for treatment

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World Journal of Gastroenterology 2007年第29期13卷 3909-3917页

作者： Adam Deane Marianne J Chapman Robert J Fraser Laura K Bryant Carly Burgstad Nam Q Nguyen Intensive Care Unit Royal Adelaide Hospital Adelaide South Australia Discipline of Medicine University of Adelaide and Investigation and Procedures Unit Repatriation General Hospital Adelaide South Australia Investigation and Procedures Unit Repatriation General Hospital Adelaide South Australia Department of Gastroenterology and Hepatology Royal Adelaide Hospital Adelaide South Australia

Malnutrition is associated with poor outcomes in critically ill patients. Although nutritional support is yet to be proven to improve mortality in non-malnourished critically ill patients, early enteral feeding is considered best practice. However, enteral feeding is often limited by delayed gastric emptying. The best method to clinically identify delayed gastric emptying and feed intolerance is unclear. gastric residual volume （GRV） measured at the bedside is widely used as a surrogate marker for gastric emptying, but the value of GRV measurement has recently been disputed. While the mechanisms underlying delayed gastric emptying require further investigation, recent research has given a better appreciation of the pathophysiology. A number of pharmacological strategies are available to improve the success of feeding. Recent data suggest a combination of intravenous metoclopramide and en/thromycin to be the most successful treatment, but novel drug therapies should be explored. Simpler methods to access the duodenum and more distal small bowel for feed delivery are also under investigation. This review summarises current understanding of the factors responsible for, and mechanisms underlying feed intolerance in critical illness, together with the evidence for current practices. Areas requiring further research are also highlighted.

关键词： Critical illness Enteral nutrition gastric emptying gastric motility Gastrointestinal hormones Metoclopramide Erythromycin Prokinetic therapy

Study on functional connections between supraoptic nucleus and stomach in rats

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Study on functional connections between supraoptic nucleus a...

Loss of gastric ICC accompanied by up-regulation of RAS signaling pathways in STZ-induced diabetic mice

中国生理学会第23届全国会员代表大会暨生理学学术大会

作者： Chang-Liang LU,Zhao-Ping LI,Jian-Ping ZHU,Dong-Qin ZHAO,Hong-Bin AI~* College of Life Sciences,Shandong Normal University,Jinan,250014

＜正＞Objective:Many evidences support the standpoint that there are functional connections between the hypothalamic paraventricular nucleus（PVN） and the stomach,then what about the supraoptic nucleus（SON） which is similar with the PVN in the localization and the neurons organization is *** question was probed in the present ***:The rats were anesthetized and then divided into four groups randomly. GroupⅠ,the neuronal discharge was recorded extracellularly in the NTS,DMV or SON before and after the cold normal saline（4℃） was perfused into the stomach from esophagus and effused from the duodenum for 5 min. GroupⅡ,the rats were stimulated by cold saline as GroupⅠ,and 60 min later,the Fos expression of the NTS,DMV and SON was examined via immunohistochemistry technique,***Ⅲwas the control to GroupⅡand was not perfused with cold saline（4℃）.GroupⅣ,gastric motility was recorded continuously by inserting a latex balloon into pylorus through the forestomach which connected with pressure *** the amplitude, duration,frequency and motility index of gastric contraction waves within 10 min before and after microinjection of L-Glu into the SON were *** data represent the mean±***:In GroupⅠ,the discharge frequency caused by the gastric lower temperature increased in all the three nuclei,but differed in *** and SON had significant difference（P＜0.05） than before the perfusion of cold saline[e.g.,SON,（6.85±1.71） spikes/s vs （4.5±0.68） spikes/s,n=7],but NTS had no significant *** GroupⅡ,Fos expression in NTS,DMV and SON was respectively greater than that of GroupⅢ（P＜0.05 or＜0.01）（*** SON,the number of Fos-positive neurons is 188.23±16.45 vs 102.82±7.39,n=5）.In GroupⅣ,microinjection of L-Glu（5 nmol/L,n=7） into SON significantly inhibited gastric motility,motility index before injection was 1482.1±708.2 and 1185.5±639.2 after injection （P＜0.05）.Conclusion:These data strongly suggest that there are functional c

关键词： supraoptic nucleus neuronal discharge c-Fos expression gastric motility

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Loss of gastric ICC accompanied by up-regulation of RAS sign...