Full Young Chang

A prospective, randomized trial of endoscopic hemoclip versus heater probe thermocoagulation for peptic ulcer bleeding

A prospective, randomized trial of endoscopic hemoclip versus heater probe thermocoagulation for peptic ulcer bleeding

Asian Consensus Report on Functional Dyspepsia

Background/Aims Environmental factors such as food, lifestyle and prevalence of Helicobacter pylori infection are widely different in Asian countries compared to the West, and physiological functions and genetic factors of Asians may also be different from those of Westerners. Establishing an Asian consensus for functional dyspepsia is crucial in order to attract attention to such data from Asian countries, to articulate the experience and views of Asian experts, and to provide a relevant guide on management of functional dyspepsia for primary care physicians working in Asia. Methods Consensus team members were selected from Asian experts and consensus development was carried out using a modified Delphi method. Consensus teams collected published papers on functional dyspepsia especially from Asia and developed candidate consensus statements based on the generated clinical questions. At the first face-to-face meeting, each statement was reviewed and e-mail voting was done twice. At the second face-to-face meeting, final voting on each statement was done using keypad voting system. A grade of evidence and a strength of recommendation were applied to each statement according to the method of the GRADE Working Group. Results Twenty-nine consensus statements were finalized, including 7 for definition and diagnosis, 5 for epidemiology, 9 for pathophysiology and 8 for management. Algorithms for diagnosis and management of functional dyspepsia were added. Conclusions This consensus developed by Asian experts shows distinctive features of functional dyspepsia in Asia and will provide a guide to the diagnosis and management of functional dyspepsia for Asian primary care physicians.

Spinal Microglia Initiate and Maintain Hyperalgesia in a Rat Model of Chronic Pancreatitis

BACKGROUND & AIMSnThe chronic, persistent pain associated with chronic pancreatitis (CP) has many characteristics of neuropathic pain, initiated and maintained by the activation of spinal microglia. We investigated whether activated microglia in the thoracic spinal cord contribute to chronic pain in a rat model of CP.nnnMETHODSnCP was induced in Sprague-Dawley rats by an intraductal injection of 2% trinitrobenzene sulfonic acid. Hyperalgesia was assessed by the measurement of mechanical sensitivity of the abdomen and nocifensive behavior to electrical stimulation of the pancreas. Three weeks after induction of CP, spinal samples were analyzed by immunostaining and immunoblot analyses for levels of CD11 (a marker of microglia, determined with the antibody OX42) and phosphorylated p38 (P-p38, a marker of activation of p38 mitogen-activated protein kinase signaling). We examined the effects of minocycline (inhibitor of microglia) and fractalkine (microglia-activating factor) on visceral hyperalgesia in rats with CP.nnnRESULTSnRats with CP had increased sensitivity and nociceptive behaviors to mechanical probing of the abdomen and electrical stimulation of the pancreas. The dorsal horn of the thoracic spinal cords of rats with CP contained activated microglia (based on increased staining with OX42), with an ameboid appearance. Levels of P-p38 increased in rats with CP and colocalized with OX42-positive cells. Intrathecal injection of minocycline reversed and prevented the increase of nocifensive behaviors and levels of P-p38 in rats with CP. Fractalkine induced hyperalgesia in rats without CP, which was blocked by minocycline.nnnCONCLUSIONSnActivated spinal microglia have important roles in maintaining and initiating chronic pain in a rat model of CP. Microglia might be a target for treatment of hyperalgesia caused by pancreatic inflammation.

Endoscopic injection with fibrin sealant versus epinephrine for arrest of peptic ulcer bleeding: A randomized, comparative trial

Background Endoscopic epinephrine and fibrin injection in the treatment of bleeding peptic ulcer are reported to be safe, effective, and easy to use. However, a wide range of rebleeding rates has been reported with epinephrine injection. Goals To compare the hemostatic effects of endoscopic injection with fibrin sealant versus epinephrine. Study Between December 1998 and July 2000, 51 patients with active bleeding or nonbleeding visible vessels entered this trial. The clinical parameters were comparable between both groups. In the epinephrine group, we injected 5 to 10 mL of 1:10,000 epinephrine, surrounding the bleeder. In the fibrin sealant group, we injected fibrin sealant 4 mL, surrounding the bleeder. Results Initial hemostasis was obtained in all enrolled patients. Rebleeding was more in the epinephrine group than in the fibrin sealant group (4 [15%] of 26 vs. 14 [56%] of 25, p = 0.003 on the intention-to-treat basis, and 4 [16.7%] of 24 vs. 14 [58.3%] of 24, p = 0.003 on the per protocol basis, respectively). Volume of blood transfusion, number of surgeries, hospital stay, and number of deaths were similar between both groups. Conclusion Fibrin sealant injection is more effective in preventing rebleeding than epinephrine after endoscopic therapy, but this study showed no difference in outcomes with either therapy.

Inhibitory effects of isoliquiritigenin on the migration and invasion of human breast cancer cells

Introduction: Isoliquiritigenin (ISL) is a natural phenolic compound extracted from licorice. Previous studies have shown that ISL is a potent antioxidant with anti-inflammatory and antitumor activities. The anti-invasive activity of ISL was still unclear. The actual causes of death for most breast cancer patients were due to the tumor metastasis. Attenuating the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) is well known to prevent tumor metastasis. Objectives: The purpose of this study is to investigate the effects of ISL on VEGF and MMP expression in highly metastatic human breast cancer cell line, MDA-MB-231. Results: ISL reduced the secretions and protein levels of VEGF. The VEGF upstream regulatory protein, hypoxia-inducible factor 1-alpha (HIF-1α), was also reduced after ISL treatment. Moreover, ISL inhibited the expression and gelatinolytic activity of MMP-2 and MMP-9 which were confirmed by western blot and gelatin zymography assay. Additionally, the anti-migratory activity of ISL was further confirmed by chamber migration assay and wound migration assay. Upstream signaling pathways, including the expression of phosphatidylinositol-3 kinase (PI3K), the phosphorylation of p38 and Akt kinase and NF-κB DNA binding activity, were suppressed by ISL. Conclusion: These findings suggest that ISL suppresses the migration of MDA-MB-231 cells by inhibiting the upstream signaling pathways.

Estrogen rapidly modulates 5-hydroxytrytophan-induced visceral hypersensitivity via GPR30 in rats.

BACKGROUND & AIMSnSex hormones have been reported to modulate visceral hypersensitivity (VH). Estrogen regulates neurons not only by binding to estrogen receptors (ERalpha and ERbeta) to initiate transcription but also via the G-protein coupled receptor GPR30, which binds and rapidly mediates actions of estrogen. We examined the role of sex hormones in a VH model without colonic inflammation.nnnMETHODSn5-Hydroxytryptophan (5HTP) was injected subcutaneously into awake female rats to induce VH; the 5HT3 antagonist (granisetron) or saline (control) were injected 30 minutes later. Immunohistochemistry was used to quantify calcitonin gene-related peptide-immunoreactive (CGRP-IR) neurons in the dorsal root ganglion (DRG). 5HTP-induced VH was evaluated in ovariectomized rats injected with 17beta-estradiol, progesterone, or both. ER alpha/beta agonist, GPR30 agonist, ER antagonist (ICI-182,780) or GPR30 antisense oligodeoxynucleotide were given to 5HTP-primed, estrogen-treated ovariectomized rats.nnnRESULTSnRats given 5HTP had increased VH that was inhibited by granisetron, accompanied by a decrease in CGRP-IR in the DRG. Ovariectomy eliminated 5HTP-induced VH, whereas estrogen and the combination of estrogen and progesterone, but not progesterone alone, restored the VH. The GPR30 agonist, but not the ERbeta agonist, rapidly restored VH. VH was preserved by coadministration of ICI-182,780 and estrogen but was absent after administration of the GPR30 antisense oligodeoxynucleotide. GPR30 colocalized with 5HT3 in DRG neurons; no significant inflammation occurred in colonic mucosa.nnnCONCLUSIONSnIn the absence of mucosal inflammation, estrogen can rapidly modulate 5HTP-induced VH. Loss of gonad hormones suppresses VH, whereas estrogen replacement restores it. Estrogen-mediated VH appears to act through GPR30.

Changes of the neuropeptides content and gene expression in spinal cord and dorsal root ganglion after noxious colorectal distension.

Visceral pain/hypersensitivity is a cardinal symptom of functional gastrointestinal disorders. With their peripheral and central (spinal) projections, sensory neurons in the dorsal root ganglia (DRG) are the gateway for painful signals emanating from both somatic and visceral structures. In contrast to somatic pain, the neurochemical pathways involved in visceral pain/hypersensitivity have not been well studied. We hypothesized the neuropeptide changes in spinal cord and DRG during visceral pain would mirror similar changes in somatic nociception. Noxious (painful) colorectal distension (CRD) was done by distending a rectal balloon up to 60 mm Hg phasically for 1 h in Sprague-Dawley rats. The spinal content of calcitonin gene-related peptide (CGRP), substance P (SP), galanin and vasoactive intestinal peptide (VIP) as well as their mRNAs in DRG were measured at 0, 4 and 24 h after the CRD. Visceromotor reflex (VMR) was measured by recording the electromyogram at the abdominal muscle in response to CRD. Distal colorectum was removed for evaluating the presence of inflammation. No significant evidence of histological inflammation was seen in the colonic mucosa/submucosa after repeated CRD, which is confirmed by myeloperoxidase assay. The spinal content of CGRP and SP decreased significantly 4 h after CRD, while galanin and VIP levels increased gradually and reached highest level at 24 h (p<0.05). The mRNAs in DRG of the neuropeptides were significantly upregulated after CRD (p<0.05). VMR recording showed the rats colon became hypersensitive 4 h after CRD, a sequence parallel to the spinal changes of CGRP and SP in timeframe. Noxious mechanical distension of the colorectum causes an acute change in the spinal levels of excitatory neurotransmitters (CGRP and SP), probably reflecting central release of these peptides from sensory neurons and contributing to the hypersensitivity following the noxious CRD. This is followed by a slower change in the levels of the inhibitory neurotransmitter galanin and VIP. Such stimulation results in significant alternation of the gene expression in DRG, reflecting the plasticity of the neuronal response. In the absence of visceral inflammation, the aforementioned neuropeptides are important mediators in the processing of visceral pain/hypersensitivity.

Asian consensus report on functional dyspepsia

Background and Aim:u2002 Environmental factors such as food, lifestyle and prevalence of Helicobacter pylori infection are widely different in Asian countries compared with the West, and physiological functions and genetic factors of Asians may also be different from those of Westerners. Establishing an Asian consensus for functional dyspepsia is crucial in order to attract attention to such data from Asian countries, to articulate the experience and views of Asian experts, and to provide a relevant guide on management of functional dyspepsia for primary care physicians working in Asia.

Inhibition of gastric emptying and intestinal transit by amphetamine through a mechanism involving an increased secretion of CCK in male rats

1 The effect of amphetamine on gastrointestinal (GI) transit and the plasma levels of cholecystokinin (CCK) were studied in male rats. 2 Gastric emptying was inhibited both acutely and chronically by the administration of amphetamine. GI transit was decreased by the acute administration of amphetamine but not affected by the chronic administration of amphetamine. 3 Plasma CCK levels were increased dose‐dependently by amphetamine. 4 Proglumide, a CCK receptor antagonist, prevented amphetamine‐induced inhibition of gastric emptying and the decrease in GI transit in male rats. 5 The selective CCKA receptor antagonist, lorglumide, dose‐dependently attenuated the amphetamine‐induced inhibition of gastric emptying in male rats. In contrast, the selective CCKB receptor antagonist, PD 135,158, did not reverse the effect of amphetamine on gastric emptying. 6 Both lorglumide and PD 135,158 reversed the inhibitory effect of amphetamine on GI transit in male rats. 7 These results suggest that amphetamine‐induced inhibition of gastric emptying and intestinal transit is due in part to a mechanism associated with the hypersecretion of endogenous CCK.

The evaluation of otilonium bromide treatment in asian patients with irritable bowel syndrome.

Background/Aims Antispasmodics including otilonium bromide (OB) are recommended to treat irritable bowel syndrome (IBS). However, reports about OB experience in Asia is sparse. The purpose of present study was to provide the efficacy of OB in treating Asian IBS patients. Methods Overall, 117 IBS patients meeting Rome II criteria were enrolled in an 8-week, double-blind, active-controlled and single center trial. Randomized participants received either OB 40 mg or mebeverine 100 mg 3 doses daily. The primary endpoints were to evaluate the net changes of abdominal pain/discomfort frequency score (APDFS) and safety profile, while the secondary endpoints were to assess the changes in abdominal pain/discomfort intensity, flatulence, abdominal bloating, satisfied stool frequency etc. Results Finally, 49 OB and 52 mebeverine subjects were eligible for efficacy analysis. Compared to baselines in per protocol populations, the reduced APDFSs in OB and mebeverine were 0.55 ± 1.20 (P = 0.011) and 0.37 ± 1.11 (P = 0.042), respectively, to show similarly reduced scores. The most reported side effects included dry mouth, nausea and dizziness. Besides, the improved APDFSs at 4th week visit, final alleviations in abdominal pain intensity, flatulence, abdominal bloating and satisfied stool frequency with global assessments filled by both patients and investigators were significantly achieved by both treatments, and OB was not inferior to mebeverine in treating these parameters. Conclusions In Orientals, OB is as effective as mebeverine for alleviating IBS symptoms in terms of abdominal pain, flatulence, abdominal bloating etc. However, obvious side effects are also observed. A large-scaled trial and post-marketing surveillance are recommended to confirm its efficacy and safety.