(Headache 2012;52:433-440) “
“Objective.— We evaluated the influence of physician-diagnosed migraine on blood pressure levels and the risk of hypertensive disorders of pregnancy in a clinic-based prospective

cohort study of 3373 healthy pregnant women. Background.— The relationship between migraine and blood pressure is controversial with results from several studies suggesting Cobimetinib nmr positive associations, while others suggest null or inverse associations. To our knowledge, no previous study has investigated blood pressure profiles among pregnant migraineurs. Methods.— We abstracted blood pressure values and delivery information from medical records of women presenting to prenatal clinics in Washington State. Mean blood pressure differences for pregnant migraineurs and non-migraineurs were estimated in regression models, using generalized estimating equations. We calculated odds ratios and 95% confidence intervals (95% CIs) for gestational hypertension and preeclampsia in relation to migraine status. Results.— Mean first, second, and third trimester systolic blood pressures (SBP) were elevated among pregnant migraineurs as compared with non-migraineurs. Migraineurs had higher mean third trimester

SBP (4.08 mmHg) than non-migraineurs. check details Trimester-specific diastolic blood pressure (DBP) values were variably related with migraine status. Mean first (0.82 mmHg) and third (2.39 mmHg) trimester DBP were higher, and second trimester DBP values were lower (−0.24) among migraineurs as compared with non-migraineurs. Migraineurs had a 1.53-fold increased odds of preeclampsia (95% CI 1.09 to 2.16). Additionally, migraineurs who were overweight or obese had a 6.10-fold

increased odds of preeclampsia (95% CI 3.83 to 9.75) as compared with lean non-migraineurs. Conclusions.— Pregnant migraineurs had elevated blood pressures, particularly SBP measured in the third trimester, and a higher risk of preeclampsia than pregnant women without migraine. Observed associations were MCE公司 more pronounced among overweight or obese migraineurs. Our findings add to the accumulating evidence of adverse pregnancy outcomes among migraineurs. “
“During the 14th International Headache Congress the results of several innovative studies that contribute to our understanding of headache pathophysiology and treatment were presented. Here we summarize work expected to contribute substantially to understanding headache mechanisms, while an accompanying manuscript summarizes presentations regarding the treatment of headache.

3C). These observations suggest that BSEP is internalized through

a Rab5a- and dynamin-dependent process. The C-terminal tail of BSEP encompassing residue 1284-1321 contains a canonical Tyr-based signal (Y1310-Y-K-L-V) that might overlap selleck chemicals llc a leucine-based (Leu1301-M) signal. To assess these signals, we appended the seven amino acids (GAYYKLV) to the Tac molecule with an eight-alanine amino acid linker region to investigate the ability of this motif to internalize. We found that Tac-8AGAYYKLV was able to internalize into punctuate structures (Fig. 4). Mutations of Y1310Y1311 or L1313V1314 to alanines abolished the internalization of the Tac chimera and caused the protein to be retained at the plasma membrane (Fig. 4). These data demonstrated that the Y1310Y1311 and L1313V1314 amino acids are important for internalization. JNK inhibitor cost In order to investigate the relative contribution of the tyrosine-based motif compared with the leucine-based motif within the 38–amino acid C-terminal end of BSEP, we mutated Y1310Y1311 (Tac-YY), L1303M1304 (Tac-LM), or both (Tac-YYLM) to alanine residues and observed their internalization by immunofluorescence and cell ELISA. Compared with TacCterm, Tac-YY remained on the cell surface after internalization for 20 minutes at 37°C (Fig. 5A). However, the Tac–LM internalized to a similar extent as

TacCterm, indicating that these two residues do not contribute to internalization of this construct (Fig. 5A). In addition, mutating both putative motifs resulted in loss of internalization compared with TacCterm, medchemexpress similar to the Tac–YY (Fig. 5A). Quantitation of internalization of these Tac chimeras was then determined using a cell ELISA internalization assay. In HEK293T cells, 40% of cell surface TacCterm was internalized in 20 minutes, resulting in a rate of ∼2%/min (Fig. 5B). In contrast, Tac alone was internalized at a rate of ∼0.5%/min (Fig. 5B). The efficiency of internalization was completely abolished in the Y1310Y1311

mutant. Mutation of L1303M1304 did not lead to a significant decrease in internalization, confirming that the leucine-based motif does not contribute significantly to endocytosis. Therefore, the Y1310Y1311 is the predominant signal for internalization. Transfection of HEK293T cells with full-length BSEP with or without the tyrosine mutations was then carried out in order to confirm the importance of this motif in endocytosis. Immunofluorescence showed that GFP–BSEP was expressed on the cell surface in both the wild-type and mutant transfected cells (Fig. 6A). Cell surface biotinylation was used to label the BSEP before internalization and membrane stripping. Strepavidin bead pull-down demonstrated that full-length wild-type GFP–BSEP that had been expressed on the plasma membrane could be efficiently endocytosed (Fig. 6B). Densitometry of the blots revealed that this internalization occurred at a rate similar to that demonstrated with TacCterm (Supporting Fig. 2).

3C). These observations suggest that BSEP is internalized through

a Rab5a- and dynamin-dependent process. The C-terminal tail of BSEP encompassing residue 1284-1321 contains a canonical Tyr-based signal (Y1310-Y-K-L-V) that might overlap Selleck Midostaurin a leucine-based (Leu1301-M) signal. To assess these signals, we appended the seven amino acids (GAYYKLV) to the Tac molecule with an eight-alanine amino acid linker region to investigate the ability of this motif to internalize. We found that Tac-8AGAYYKLV was able to internalize into punctuate structures (Fig. 4). Mutations of Y1310Y1311 or L1313V1314 to alanines abolished the internalization of the Tac chimera and caused the protein to be retained at the plasma membrane (Fig. 4). These data demonstrated that the Y1310Y1311 and L1313V1314 amino acids are important for internalization. SB203580 research buy In order to investigate the relative contribution of the tyrosine-based motif compared with the leucine-based motif within the 38–amino acid C-terminal end of BSEP, we mutated Y1310Y1311 (Tac-YY), L1303M1304 (Tac-LM), or both (Tac-YYLM) to alanine residues and observed their internalization by immunofluorescence and cell ELISA. Compared with TacCterm, Tac-YY remained on the cell surface after internalization for 20 minutes at 37°C (Fig. 5A). However, the Tac–LM internalized to a similar extent as

TacCterm, indicating that these two residues do not contribute to internalization of this construct (Fig. 5A). In addition, mutating both putative motifs resulted in loss of internalization compared with TacCterm, MCE公司 similar to the Tac–YY (Fig. 5A). Quantitation of internalization of these Tac chimeras was then determined using a cell ELISA internalization assay. In HEK293T cells, 40% of cell surface TacCterm was internalized in 20 minutes, resulting in a rate of ∼2%/min (Fig. 5B). In contrast, Tac alone was internalized at a rate of ∼0.5%/min (Fig. 5B). The efficiency of internalization was completely abolished in the Y1310Y1311

mutant. Mutation of L1303M1304 did not lead to a significant decrease in internalization, confirming that the leucine-based motif does not contribute significantly to endocytosis. Therefore, the Y1310Y1311 is the predominant signal for internalization. Transfection of HEK293T cells with full-length BSEP with or without the tyrosine mutations was then carried out in order to confirm the importance of this motif in endocytosis. Immunofluorescence showed that GFP–BSEP was expressed on the cell surface in both the wild-type and mutant transfected cells (Fig. 6A). Cell surface biotinylation was used to label the BSEP before internalization and membrane stripping. Strepavidin bead pull-down demonstrated that full-length wild-type GFP–BSEP that had been expressed on the plasma membrane could be efficiently endocytosed (Fig. 6B). Densitometry of the blots revealed that this internalization occurred at a rate similar to that demonstrated with TacCterm (Supporting Fig. 2).

Feeding for 4d/11% models the early response to ethanol, while 25d,32% is a model of chronic ethanol consumption.19 During a 4d,32% ethanol exposure protocol, C57BL/6J wild-type (WT) mice received a once-daily intraperitoneal injection of necrostatin-1 (1.65 mg/kg) or vehicle (2% dimethyl sulfoxide in phosphate-buffered saline) before ethanol (4d,32%) feeding. This concentration/dose

regimen inhibits selleck chemicals RIP1 kinase activity in vivo.10, 20, 21 Deidentified human liver biopsy samples from 20 ALD patients and eight patients with minimal liver pathology were obtained from the Cleveland Clinic surgical pathology database. The selection criteria are described in the Supporting Information. All procedures using deidentified human liver

tissue were approved by the Cleveland Clinic Institutional Research Board. For human liver biopsies, paraffin-embedded livers were deparaffinized and stained for RIP3 as described above, except that 3-amino-9-ethylcarbazole was used instead of 3,3′-diaminobenzidine as the horseradish peroxidase–specific selleck chromogen. Omitting the primary antibody (no primary immunoglobulin G control) in this protocol abrogated the staining, demonstrating the specificity of the immunoreactive staining (data not shown). Images were acquired in a blinded manner using a 20× objective. RIP3 immunostaining was then scored by an experienced pathologist (X. Liu) taking into consideration medchemexpress staining intensity and percentage of positive cells using a scale of 0-3 (0, lack of any staining; 1, faint staining in

<10% of cells; 2, fine granular staining in 10%-50% cells or coarse granular staining in 10%-20% of cells; 3, fine granular staining in >50% cells or coarse granular staining in >20% cells). A subset of these subjects was analyzed via morphometric semiquantitation analysis using Image-Pro Plus software (n = 6 for control and n = 11 for ALD cases). Details regarding mouse liver biopsies and in situ proximity ligation assay (PLA) are given in the Supporting Information. Values shown in all figures represent the mean ± SEM (n ≥ 4 for pair-fed, n ≥ 6 for ethanol-fed). Analysis of variance was performed using the general linear models procedure (SAS, Carey, IN). Data were log-transformed as necessary to obtain a normal distribution. Follow-up comparisons were made by least square means testing. A Student t test was used for comparing values obtained from two groups (for Fig. 2 only). If RIP3-dependent necroptosis contributes to ethanol-induced liver injury, then RIP3 expression should be increased in response to ethanol feeding. To test this hypothesis, RIP3 expression was evaluated by immunohistochemistry in livers from C57BL/6 mice following 4d,11% or 4d,32% ethanol feeding and 25d,32% ethanol feeding.

2 In the liver, PC1 and PC2 are expressed by biliary epithelial cells and are located in the primary cilium of the cell. PC2, a nonselective membrane Ca2+ channel, is also

located in the endoplasmic reticulum (ER), in which it contributes to Ca2+ regulation.3, 4 Cholangiocytes lining liver cysts in patients with ADPKD show phenotypic and functional peculiarities, such as marked overexpression of vascular endothelial growth factor A (VEGF-A), angiopoietins, insulin-like growth factor 1 (IGF1), and their cognate receptors vascular endothelial growth factor receptor 2 (VEGFR2), TEK tyrosine kinase endothelial (Tie)-2, and insulin-like growth factor 1 receptor (IGF1R).5, 6 Using mice with conditional defects of PC2, we have shown that the cystic epithelium of PC2-defective mice overexpresses VEGF, which in turn stimulates cholangiocyte proliferation, BGB324 molecular weight and that the blockade of VEGFR2 signaling inhibits liver cyst growth in vivo.7 We have also shown that protein kinase A (PKA)–mediated up-regulation of ERK1/2 sustains the increased secretion of VEGF as well as its proliferative effects. IGF1 is concentrated in the fluid drained from liver cysts of ADPKD patients, and IGF1 and its main receptor IGF1R,8 along with phosphorylated protein kinase B (pAKT) and phosphorylated mammalian target of rapamycin (p-mTOR),

c-Met inhibitor are overexpressed in the cystic epithelium of human ADPKD.5 Protein kinase B (AKT) is an

inhibitor of tuberin and thereby an activator of mammalian target of rapamycin (mTOR), through which it controls hypoxia-inducible factor 1 alpha (HIF1α), the major transcriptional factor for VEGF.9 Through similar mechanisms, IGF1 up-regulates the expression of VEGF in colon cancer cells.10 Expression of mTOR is increased in the cystic epithelium of the kidney cells,11 and this suggests that the mTOR pathway may play a crucial role in the growth of kidney cysts. Rapamycin is an mTOR inhibitor that has been approved for use in humans because of its immunosuppressive properties. Rapamycin slows renal cyst development and renal function deterioration in rodent models of polycystic kidney disease.11–13 A recent retrospective study showed a reduction in liver cyst volume 上海皓元医药股份有限公司 in ADPKD patients who received sirolimus as immunosuppressive therapy after kidney transplantation.14 Recent experimental work has shown that the mTOR inhibitor rapamycin is a potent inhibitor of angiogenesis and proliferation of endothelial, cancer, and stromal cells.15, 16 We hypothesized that inhibition of mTOR by rapamycin could block the progression of polycystic liver disease by interfering with IGF1 and VEGF autocrine signaling. We tested this hypothesis in conditional polycystin-2–knockout (Pkd2KO) mice, which overexpress VEGF, VEGFR2, and IGF1 in a manner similar to human ADPKD.

2 In the liver, PC1 and PC2 are expressed by biliary epithelial cells and are located in the primary cilium of the cell. PC2, a nonselective membrane Ca2+ channel, is also

located in the endoplasmic reticulum (ER), in which it contributes to Ca2+ regulation.3, 4 Cholangiocytes lining liver cysts in patients with ADPKD show phenotypic and functional peculiarities, such as marked overexpression of vascular endothelial growth factor A (VEGF-A), angiopoietins, insulin-like growth factor 1 (IGF1), and their cognate receptors vascular endothelial growth factor receptor 2 (VEGFR2), TEK tyrosine kinase endothelial (Tie)-2, and insulin-like growth factor 1 receptor (IGF1R).5, 6 Using mice with conditional defects of PC2, we have shown that the cystic epithelium of PC2-defective mice overexpresses VEGF, which in turn stimulates cholangiocyte proliferation, Selleckchem PLX3397 and that the blockade of VEGFR2 signaling inhibits liver cyst growth in vivo.7 We have also shown that protein kinase A (PKA)–mediated up-regulation of ERK1/2 sustains the increased secretion of VEGF as well as its proliferative effects. IGF1 is concentrated in the fluid drained from liver cysts of ADPKD patients, and IGF1 and its main receptor IGF1R,8 along with phosphorylated protein kinase B (pAKT) and phosphorylated mammalian target of rapamycin (p-mTOR),

http://www.selleckchem.com/products/cx-4945-silmitasertib.html are overexpressed in the cystic epithelium of human ADPKD.5 Protein kinase B (AKT) is an

inhibitor of tuberin and thereby an activator of mammalian target of rapamycin (mTOR), through which it controls hypoxia-inducible factor 1 alpha (HIF1α), the major transcriptional factor for VEGF.9 Through similar mechanisms, IGF1 up-regulates the expression of VEGF in colon cancer cells.10 Expression of mTOR is increased in the cystic epithelium of the kidney cells,11 and this suggests that the mTOR pathway may play a crucial role in the growth of kidney cysts. Rapamycin is an mTOR inhibitor that has been approved for use in humans because of its immunosuppressive properties. Rapamycin slows renal cyst development and renal function deterioration in rodent models of polycystic kidney disease.11–13 A recent retrospective study showed a reduction in liver cyst volume medchemexpress in ADPKD patients who received sirolimus as immunosuppressive therapy after kidney transplantation.14 Recent experimental work has shown that the mTOR inhibitor rapamycin is a potent inhibitor of angiogenesis and proliferation of endothelial, cancer, and stromal cells.15, 16 We hypothesized that inhibition of mTOR by rapamycin could block the progression of polycystic liver disease by interfering with IGF1 and VEGF autocrine signaling. We tested this hypothesis in conditional polycystin-2–knockout (Pkd2KO) mice, which overexpress VEGF, VEGFR2, and IGF1 in a manner similar to human ADPKD.

Oncogenic viruses alter the proteasomal activity of target cells, affecting viral entry, replication, and release and enhancing cell survival.31 Targeting of proteins to the proteasome through interactions with ubiquitin ligases is essential for normal protein turnover. In this context, HBx is able to down-regulate both proteasome26 and ubiquitin

ligase functions.6 Our data show that HBx induces a marked accumulation of PTTG1 protein by reducing its ubiquitination and subsequent degradation. It has been demonstrated that the SCF ubiquitin ligase complex is involved in the degradation of phosphorylated forms of PTTG1 in nonmitotic cells. In addition, HBx affects SCF ubiquitin ligase functions through mechanisms involving protein–protein interactions.6 Confocal microscopy analysis and biochemical data strongly suggest that HBx may interact with both the SCF component Cul1 and PTTG1. Interestingly, the association between PTTG1 and Cul1 CHIR99021 is disrupted in the presence of HBx. However, HBx expression does not enhance PTTG1 accumulation after Cul1 silencing. Together, these data suggest that HBx may alter the

formation of the SCF/PTTG1 complex, leading to an impairment of PTTG1 ubiquitination. Thus, in the presence of HBx, PTTG1 is not targeted to proteasome-mediated degradation resulting in an abnormal protein accumulation (Fig. 8). It is tempting to speculate that by affecting the normal turnover of PTTG1, HBx could alter some of the PTTG1-related functions and promote cellular transformation. The SCF ubiquitin ligases are mammalian cullin RING ubiquitin ligases in which F-box proteins provide selleck screening library the substrate targeting specificity of the complex. Skp2 is the F-box protein that targets key regulatory proteins, such as c-myc, for degradation.32 Interestingly, it has been shown that HBx is able to block ubiquitination of c-myc through a direct interaction with Skp2 and destabilization of the SCF/Skp2 complex. An association between HBx-mediated PTTG1 stabilization and HBx/Skp2 interaction may also exist,

but this issue requires further study. PP2A is an important serine/threonine phosphatase family involved in essential cellular processes such as cell division, gene regulation, protein synthesis, and cytoskeleton organization. PP2A 上海皓元医药股份有限公司 enzymes typically exist as heterotrimers comprising a common catalytic subunit (PP2Ac) and different structural and regulatory subunits.33 It has been shown that hepatotropic viruses, including hepatitis C virus and HBV, alter PP2Ac activity.34 HBx protein is the most likely candidate responsible for HBV-mediated PP2Ac modulation.34 Our results show that HBx promotes PTTG1 accumulation, inhibiting the degradation of phosphorylated forms of PTTG1 after chemical inhibition of PP2A. Further experiments are necessary to analyze whether HBx could affect PTTG1 expression levels by up-regulating PP2A activity.

Oncogenic viruses alter the proteasomal activity of target cells, affecting viral entry, replication, and release and enhancing cell survival.31 Targeting of proteins to the proteasome through interactions with ubiquitin ligases is essential for normal protein turnover. In this context, HBx is able to down-regulate both proteasome26 and ubiquitin

ligase functions.6 Our data show that HBx induces a marked accumulation of PTTG1 protein by reducing its ubiquitination and subsequent degradation. It has been demonstrated that the SCF ubiquitin ligase complex is involved in the degradation of phosphorylated forms of PTTG1 in nonmitotic cells. In addition, HBx affects SCF ubiquitin ligase functions through mechanisms involving protein–protein interactions.6 Confocal microscopy analysis and biochemical data strongly suggest that HBx may interact with both the SCF component Cul1 and PTTG1. Interestingly, the association between PTTG1 and Cul1 BI2536 is disrupted in the presence of HBx. However, HBx expression does not enhance PTTG1 accumulation after Cul1 silencing. Together, these data suggest that HBx may alter the

formation of the SCF/PTTG1 complex, leading to an impairment of PTTG1 ubiquitination. Thus, in the presence of HBx, PTTG1 is not targeted to proteasome-mediated degradation resulting in an abnormal protein accumulation (Fig. 8). It is tempting to speculate that by affecting the normal turnover of PTTG1, HBx could alter some of the PTTG1-related functions and promote cellular transformation. The SCF ubiquitin ligases are mammalian cullin RING ubiquitin ligases in which F-box proteins provide see more the substrate targeting specificity of the complex. Skp2 is the F-box protein that targets key regulatory proteins, such as c-myc, for degradation.32 Interestingly, it has been shown that HBx is able to block ubiquitination of c-myc through a direct interaction with Skp2 and destabilization of the SCF/Skp2 complex. An association between HBx-mediated PTTG1 stabilization and HBx/Skp2 interaction may also exist,

but this issue requires further study. PP2A is an important serine/threonine phosphatase family involved in essential cellular processes such as cell division, gene regulation, protein synthesis, and cytoskeleton organization. PP2A medchemexpress enzymes typically exist as heterotrimers comprising a common catalytic subunit (PP2Ac) and different structural and regulatory subunits.33 It has been shown that hepatotropic viruses, including hepatitis C virus and HBV, alter PP2Ac activity.34 HBx protein is the most likely candidate responsible for HBV-mediated PP2Ac modulation.34 Our results show that HBx promotes PTTG1 accumulation, inhibiting the degradation of phosphorylated forms of PTTG1 after chemical inhibition of PP2A. Further experiments are necessary to analyze whether HBx could affect PTTG1 expression levels by up-regulating PP2A activity.

prevalence and associated factors Presenting Author: JIN TAO Additional Authors: XIUQING WEI, YANPING LIANG, BIN WU Corresponding Author: JIN TAO Affiliations: 4th Affiliated Hospital of Sun Yat-Sen University, 4th Affiliated Hospital of Sun Yat-Sen University, 3rd Affiliated Hospital Tyrosine Kinase Inhibitor Library of Sun Yat-Sen University Objective: To study the effect of biological feedback treatment of the outlet obstructive constipation. Methods: A analysis of the clinical data of 56 cases of biological feedback treatment of the outlet obstructive constipation was made. Results: Among 54 cases who completed the biological feedback treatment, the results of rectal manometer detection

in 35 cases indicated that the rectum sensitivity threshold and the maximum tolerance capacity and recto-anal inhibitory reflex decreased, compared with those before treatment. Paradoxical contraction of pelvic floor disappeared and normal bowel movement was regained;in cases the symptoms were improved, including times of bowel GSK126 in vitro movement, functional

constipation and anorectic distention. The effective rate of biofeedback treatment was 92.6%. Only 4 cases were ineffective and 2 cases stopped treatment. Conclusion: The short-term effect of biological feedback treatment for the outlet obstructive constipation is satisfactory, and has advantages of low cost and no need for hospital admission. Key Word(s): 1. outlet obstructive constipation; 2. biological feedback treatment; 3. functional constipation Presenting Author: YAN WANG Additional Authors: YAN WANG, HAI TAO SHI, FEN RONG CHEN, JU HUI ZHAO,

HONG LI, JIONG JIANG Corresponding Author: YAN WANG Affiliations: Second Hospital of Xi’An Jiaotong University, Second Hospital of Xi’An Jiaotong University, Second Hospital of Xi’An Jiaotong University, Second Hospital of Xi’An Jiaotong University, Second Hospital of Xi’An Jiaotong University, Second Hospital of Xi’An Jiaotong University MCE Objective: The central effects and mechanism of ghrelin on the small intestinal motility are not clear. Our study aimed to explore the effects and mechanism of ghrelin after intracerebroventricular (ICV) injection on the interdigestive myoelectric complex (IMC) in rats. Methods: (1) In the electrophysiologic experiment, two pairs of silver electrodes were implanted in the duodenum and jejunum. Rats were received ICV injection of ghrelin (6.4 μg kg −1) during fasting. Some rats were pretreated with intravenous injection of phentolamine, propranolol and atropine respectively. Other groups of rats were received ICV injection of anti-neuropeptide Y (NPY) IgG and (D-Lys3) GHRP-6 before ghrelin injected. (2) The c-Fos activation on the central nervous system (CNS) and enteric nervous system (ENS) through ICV injection of ghrelin was studied by the immunohistochemistry. Results: (1) Ghrelin showed an excitatory effect on the IMC. This effect was inhibited by atropine, anti-NPY IgG and (D-Lys3) GHRP-6, but not by propranolol and phentolamine.

prevalence and associated factors Presenting Author: JIN TAO Additional Authors: XIUQING WEI, YANPING LIANG, BIN WU Corresponding Author: JIN TAO Affiliations: 4th Affiliated Hospital of Sun Yat-Sen University, 4th Affiliated Hospital of Sun Yat-Sen University, 3rd Affiliated Hospital selleckchem of Sun Yat-Sen University Objective: To study the effect of biological feedback treatment of the outlet obstructive constipation. Methods: A analysis of the clinical data of 56 cases of biological feedback treatment of the outlet obstructive constipation was made. Results: Among 54 cases who completed the biological feedback treatment, the results of rectal manometer detection

in 35 cases indicated that the rectum sensitivity threshold and the maximum tolerance capacity and recto-anal inhibitory reflex decreased, compared with those before treatment. Paradoxical contraction of pelvic floor disappeared and normal bowel movement was regained;in cases the symptoms were improved, including times of bowel see more movement, functional

constipation and anorectic distention. The effective rate of biofeedback treatment was 92.6%. Only 4 cases were ineffective and 2 cases stopped treatment. Conclusion: The short-term effect of biological feedback treatment for the outlet obstructive constipation is satisfactory, and has advantages of low cost and no need for hospital admission. Key Word(s): 1. outlet obstructive constipation; 2. biological feedback treatment; 3. functional constipation Presenting Author: YAN WANG Additional Authors: YAN WANG, HAI TAO SHI, FEN RONG CHEN, JU HUI ZHAO,

HONG LI, JIONG JIANG Corresponding Author: YAN WANG Affiliations: Second Hospital of Xi’An Jiaotong University, Second Hospital of Xi’An Jiaotong University, Second Hospital of Xi’An Jiaotong University, Second Hospital of Xi’An Jiaotong University, Second Hospital of Xi’An Jiaotong University, Second Hospital of Xi’An Jiaotong University 上海皓元 Objective: The central effects and mechanism of ghrelin on the small intestinal motility are not clear. Our study aimed to explore the effects and mechanism of ghrelin after intracerebroventricular (ICV) injection on the interdigestive myoelectric complex (IMC) in rats. Methods: (1) In the electrophysiologic experiment, two pairs of silver electrodes were implanted in the duodenum and jejunum. Rats were received ICV injection of ghrelin (6.4 μg kg −1) during fasting. Some rats were pretreated with intravenous injection of phentolamine, propranolol and atropine respectively. Other groups of rats were received ICV injection of anti-neuropeptide Y (NPY) IgG and (D-Lys3) GHRP-6 before ghrelin injected. (2) The c-Fos activation on the central nervous system (CNS) and enteric nervous system (ENS) through ICV injection of ghrelin was studied by the immunohistochemistry. Results: (1) Ghrelin showed an excitatory effect on the IMC. This effect was inhibited by atropine, anti-NPY IgG and (D-Lys3) GHRP-6, but not by propranolol and phentolamine.