Prunolactones A-G, proangiogenic isocoumarin derivatives with an unusual 6/6/6/6/6 spiropentacyclic skeleton from the endophytic fungus Phomopsis prunorum.

Seven novel isocoumarins, prunolactones A-G (1-7), featuring an unusual 6/6/6/6/6 spiropentacyclic skeleton, together with two biosynthetic precursors phomopsilactone (8) and methyl 3-epi-shikimate (9), were isolated from the endophytic fungus Phomopsis prunorum guided by UPLC-QTOF-MS and 1H NMR spectroscopic analytical techniques. Their structures including absolute configurations of 1-7 were elucidated based on extensive spectroscopic data, X-ray diffraction analysis, and ECD calculations. Biogenetically, compounds 1-7 are proposed to be derived from polyketide and shikimate pathways via key intermolecular Diels - Alder reactions. Compounds 2, 3, and 7 showed significant in vivo proangiogenic activity in transgenic zebrafish.

Helicobacter pylori infection is associated with reduced risk of Barrett's esophagus: a meta-analysis and systematic review.

BACKGROUND: Helicobacter pylori (Hp) is a class I carcinogen in gastric carcinogenesis, but its role in Barrett's esophagus (BE) is unknown. Therefore, we aimed to explore the possible relationship. METHODS: We reviewed observational studies published in English until October 2019. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for included studies. RESULTS: 46 studies from 1505 potential citations were eligible for inclusion. A significant inverse relationship with considerable heterogeneity was found between Hp (OR = 0.70; 95% CI, 0.51-0.96; P = 0.03) and BE, especially the CagA-positive Hp strain (OR = 0.28; 95% CI, 0.15-0.54; P = 0.0002). However, Hp infection prevalence was not significantly different between patients with BE and the gastroesophageal reflux disease (GERD) control (OR = 0.99; 95% CI, 0.82-1.19; P = 0.92). Hp was negatively correlated with long-segment BE (OR = 0.47; 95% CI, 0.25-0.90; P = 0.02) and associated with a reduced risk of dysplasia. However, Hp had no correlated with short-segment BE (OR = 1.11; 95% CI, 0.78-1.56; P = 0.57). In the present infected subgroup, Hp infection prevalence in BE was significantly lower than that in controls (OR = 0.69; 95% CI, 0.54-0.89; P = 0.005); however, this disappeared in the infection history subgroup (OR = 0.88; 95% CI, 0.43-1.78; P = 0.73). CONCLUSIONS: Hp, especially the CagA-positive Hp strain, and BE are inversely related with considerable heterogeneity, which is likely mediated by a decrease in GERD prevalence, although this is not observed in the absence of current Hp infection.

Berberine alleviates visceral hypersensitivity in rats by altering gut microbiome and suppressing spinal microglial activation.

Accumulating evidence shows that agents targeting gut dysbiosis are effective for improving symptoms of irritable bowel syndrome (IBS). However, the potential mechanisms remain unclear. In this study we investigated the effects of berberine on the microbiota-gut-brain axis in two rat models of visceral hypersensitivity, i.e., specific pathogen-free SD rats subjected to chronic water avoidance stress (WAS) and treated with berberine (200 mg· kg-1 ·d-1, ig, for 10 days) as well as germ-free (GF) rats subjected to fecal microbiota transplantation (FMT) from a patient with IBS (designated IBS-FMT) and treated with berberine (200 mg· kg-1 ·d-1, ig, for 2 weeks). Before the rats were sacrificed, visceral sensation and depressive behaviors were evaluated. Then colonic tryptase was measured and microglial activation in the dorsal lumbar spinal cord was assessed. The fecal microbiota was profiled using 16S rRNA sequencing, and short chain fatty acids (SCFAs) were measured. We showed that berberine treatment significantly alleviated chronic WAS-induced visceral hypersensitivity and activation of colonic mast cells and microglia in the dorsal lumbar spinal cord. Transfer of fecal samples from berberine-treated stressed donors to GF rats protected against acute WAS. FMT from a patient with IBS induced visceral hypersensitivity and pro-inflammatory phenotype in microglia, while berberine treatment reversed the microglial activation and altered microbial composition and function and SCFA profiles in stools of IBS-FMT rats. We demonstrated that berberine did not directly influence LPS-induced microglial activation in vitro. In both models, several SCFA-producing genera were enriched by berberine treatment, and positively correlated to the morphological parameters of microglia. In conclusion, activation of microglia in the dorsal lumbar spinal cord was involved in the pathogenesis of IBS caused by dysregulation of the microbiota-gut-brain axis, and the berberine-altered gut microbiome mediated the modulatory effects of the agent on microglial activation and visceral hypersensitivity, providing a potential option for the treatment of IBS.

[Progresses on the effects and mechanisms of stress on gut microbiota].

Stress is the non-specific systemic response that occurs when the body is stimulated by various factors, and it can affect multiple systems of the body. Recent studies have shown that gut microbiota is an essential part of human microecology, and plays a pivotal role in keeping the body healthy. Stress can result in gut dysbiosis by affecting the function of intestinal mucosal barrier, intestinal immune and gastrointestinal motility. This article reviewed the alteration of gut microbiota caused by stress and the possible mechanisms involved.

Cognitive Changes in Peritoneal Dialysis Patients: A Multicenter Prospective Cohort Study.

RATIONALE & OBJECTIVE: Cognitive impairment is an independent predictor of technique failure and mortality in patients on peritoneal dialysis (PD) therapy. We investigated changes in cognitive function and factors associated with it in this population. STUDY DESIGN: Multicenter prospective cohort study. SETTING & PARTICIPANTS: 458 PD patients were enrolled and followed up for 2 years. PREDICTORS: Global and specific domains of cognitive function were measured at baseline and after 2 years. The Modified Mini-Mental State Examination (3MS) was used for assessment of global cognitive function; Trail-Making Tests A and B, for executive function; and subtests of the Battery for the Assessment of Neuropsychological Status, for immediate and delayed memory, visuospatial skill, and language ability. OUTCOMES: The primary outcome was change in cognitive function. Secondary outcomes included all-cause mortality, cardiovascular mortality, hospitalization, and transition to hemodialysis therapy. ANALYTICAL APPROACH: Multivariable linear regression models. RESULTS: The prevalence of cognitive impairment increased from 19.8% to 23.9%. 3MS scores significantly decreased (84.8 to 83.1), although executive function, immediate memory, and visuospatial skill improved over time. Delayed memory capacity and language ability were unchanged. Lower serum albumin level was associated with deteriorated delayed memory, visuospatial skill, and language ability, as well as with the decline in general cognitive function (ß values of 0.64, 0.90, 0.80, and 0.44, respectively). Advanced age, lower education, and depression were also correlated with deterioration in general and specific cognitive function. After multivariable adjustment, both global and specific cognitive impairment at baseline were associated with a greater rate of hospitalization, and memory dysfunction was associated with a lower dialysis modality survival rate. LIMITATIONS: A relatively short observation period, small number of deaths, and potential selection bias due to patients unavailable for the second assessment. CONCLUSIONS: In a PD population, global cognitive function declined over 2 years, though some specific cognitive domains improved. Besides well-recognized factors, hypoalbuminemia and depression were also risk factors for cognitive impairment.

Depression and Cognitive Impairment in Peritoneal Dialysis: A Multicenter Cross-sectional Study.

BACKGROUND: Depression and cognitive impairment have been identified as independent risk factors for mortality in peritoneal dialysis (PD) patients. The relationship between depression and global and specific cognitive functions in PD patients was investigated in this study. STUDY DESIGN: Multicenter cross-sectional study. SETTING & PARTICIPANTS: 458 clinically stable patients, drawn from 5 PD units, who performed PD for at least 3 months were enrolled. PREDICTOR: Depression, defined as depression severity index score > 0.5 using the Zung Self-rating Depression Scale. OUTCOMES: Global and specific cognitive impairment. Global cognitive function was measured using the Modified Mini-Mental State Examination (3MS), Trail-Making Test forms A and B for executive function, and subtests of the Battery for the Assessment of Neuropsychological Status for immediate and delayed memory, visuospatial skills, and language ability. RESULTS: Prevalences of depression and cognitive impairment evaluated by the 3MS were 52% and 28.4%, respectively. Patients with mild or moderate/severe depression had higher prevalences of general cognitive impairment, executive dysfunction, and impaired immediate and delayed memory. After adjusting for demographics, comorbid conditions, and clinical parameters, depression scores were independently associated with lower 3MS scores, lower immediate and delayed memory and language ability scores, and longer completion times of Trails A and B. Even mild depression was independently associated with higher risk for cognitive impairment, executive dysfunction, and impaired immediate and delayed memory after multivariable adjustments. LIMITATIONS: The causal relationship between depression and cognitive impairment could not be determined, and the potential copathogenesis behind depression and cognitive impairment was not fully investigated. CONCLUSIONS: Even mild depression is closely associated with global and specific cognitive impairment in PD patients.

Exploring the potential causal effects of food preferences on irritable bowel syndrome risk: A two-sample Mendelian randomization study.

OBJECTIVES: Irritable bowel syndrome (IBS) is a common disorder in gut-brain interaction. Diet plays an important role in the pathophysiology of IBS. Therefore, we aimed to explore the potential causal effects of food-liking on IBS to provide better diet advice for patients. METHODS: Single-nucleotide polymorphisms associated with food-liking were selected as instrumental variables, which were obtained from the latest genome-wide association study (GWAS) conducted on 161 625 participants. The summary data of genetic associations with IBS were obtained from a recent GWAS with 433 201 European controls and 53 400 cases. We used inverse variance weighting as the main analysis. Sensitivity analyses were conducted to detect horizontal pleiotropy and heterogeneity. RESULTS: Significant evidence revealed the protective effects of a vegetarian diet-liking on IBS, including asparagus, avocadoes, globe artichoke, aubergine, and black olives, while onion-liking showed potential deleterious effects. For meat and fish, preference for sardines and fried fish was marginally associated with IBS risk, but salami and salmon were potential protective factors. In terms of desserts and dairy products, preferences for cake icing, ketchup, and cheesecake were suggestively associated with higher IBS risk, while goat cheese-liking was marginally correlated with lower IBS risk. Additionally and suggestively, significant causal effects of IBS on increased preferences for globe artichoke and salami were also found in a reverse Mendelian randomization (MR) study. CONCLUSION: Our study revealed potential causal associations between food preference and IBS from a genetic perspective, which provides a dietary reference for such patients.

[The characteristics of anorectal manometry in Parkinson's disease with constipation and functional constipation].

OBJECTIVE: To investigate the discrepancy of anorectal function in patients of Parkinson's disease (PD) with constipation and functional constipation (FC). METHODS: Fifteen consecutive male PD patients with constipation and 45 male FC patients were recruited for the study. All subjects underwent colonoscopy or barium enema in order to exclude organic colon diseases. Every patient underwent anorectal manometry and was categorized into subgroups of either dyssynergia defecation (F3a) or inadequate defecatory propulsion (F3b). RESULTS: The ages of PD with constipation and FC patients were (70 ± 11) and (68 ± 11) years old respectively. The rectal resting pressure in PD with constipation was higher than that in FC group without statistical significance [9.0(4.0, 15.0) mm Hg vs 6.0(3.0, 9.5) mm Hg, P = 0.082, 1 mm Hg = 0.133 kPa]. The anal resting pressure in PD group was not different from FC group [(51.2 ± 17.2) mm Hg vs (59.7 ± 20.4) mm Hg, P = 0.152]. During anal squeezing, the maximal contraction pressure and area under the squeeze curve in PD with constipation group were both significantly lower than FC patients [maximal contraction pressure: (136.9 ± 43.8) mm Hg vs (183.0 ± 62.1) mm Hg, P = 0.010; area under the squeeze curve: (823.5 ± 635.7) mm Hg·s vs (1392.4 ± 939.9) mm Hg·s, P = 0.033]. During forced defecation, both of the defecation rectal pressure and defecation anal pressure in PD with constipation group were significantly lower than that of FC patients [22.0(15.0, 30.0) vs 42.0(31.0, 55.0) mm Hg, P = 0.000; and (46.3 ± 23.3) vs (77.9 ± 35.1) mm Hg, P = 0.002]. The proportions of F3a subtype were 10/15 and 46.7% (21/45) in PD with constipation and FC patients respectively. There was no significant difference in the constituent ratio (P = 0.120). Initial rectal sensory volumes were (91.3 ± 56.9) ml and (67.2 ± 38.9) ml in PD with constipation and FC patients respectively. Even both volumes were higher than the normal controls, there was no significant difference between the two groups (P = 0.074). CONCLUSIONS: Both PD with constipation and FC patients have abnormal anorectal motility and sensation comparing to the FC group, the parameters of anal contraction and defecation are significantly lower, F3b is dominant, and rectal sensory threshold is higher in PD with constipation patients. These parameters could possibly characterize the anorectal manometry for PD with constipation patients, which is helpful to understand the pathogenesis of PD and differentiate from other diseases.

[Reconstitution of mast cell population in gastrointestinal tract by bone marrow transplantation in mast cell deficient rats].

OBJECTIVE: To explore whether bone marrow transplantation (BMT) can restore gastrointestinal mast cells in mast cell deficient (Ws/Ws) rats and understand the features of these reconstituted mast cells. METHODS: Thirty-six Ws/Ws rats were subjected to Co(60) radiation at 6 gradient doses (6.0, 7.0, 8.0, 9.0, 10.0 and 11.0 Gy, n = 6) to confirm the appropriate dosage. And another 6 rats served as non-radiated controls. Sixteen Ws/Ws rats were exposed to a 7.5 Gy radiation and sacrificed at Day 1, 5, 8 and 12 (n = 4) to obtain hemogram and myelogram. And 4 non-radiated Ws/Ws rats served as control. Ws/Ws rats received an intravenous injection of bone marrow cells harvested from healthy congenic Brown Norway (BN) rats after a dosage of 7.5 Gy radiation. Y-chromosome fluorescence in situ hybridization (Y-FISH) was used to identify the survival and differentiation of bone marrow cells of male BN rats in female BMT-Ws/Ws rats (n = 4). Another set of 24 male BMT-Ws/Ws rats were sacrificed Weeks 5, 8, 13 and 23 post-BMT (n = 6). Tissues from esophagus, stomach, ileum and colon were harvested to perform mast cell quantification by Alcian blue staining. And mast cell derived proteinases (tryptase and chymase) were quantified by Western blotting. RESULTS: Y-FISH showed bone marrow cells from male BN rats survived in female BMT-Ws/Ws rats and mast cells were restored in gastrointestinal tract. Compared with control, the highest level of mast cell number (103 ± 6) vs (35 ± 4)/mm(2) for esophagus, (271 ± 23) vs (124 ± 13)/mm(2) for stomach, (200.1 ± 13.3) vs (103.2 ± 6.6)/mm(2), all P < 0.05) and mast cell proteinases (1.3 ± 0.3 vs 0.6 ± 0.2 for esophagus, 3.6 ± 0.8 vs 1.9 ± 0.4 for ileum, both P < 0.05) in BMT-Ws/Ws rats were observed at Week 8 post-BMT. The number of mast cell and proteinases decreased at Week 13 post-BMT. CONCLUSIONS: BMT may restore mast cells in Ws/Ws rats. The best time period for using BMT-Ws/Ws rats in the study of mast cell function is between Weeks 8-13 post-BMT.

[In vitro metabolism of fenbendazole prodrug].

Synthesized fenbendazole prodrug N-methoxycarbonyl-N'-(2-nitro-4-phenylthiophenyl) thiourea (MPT) was analyzed in vitro in artificial gastric juice, intestinal juice and mouse liver homogenate model by using HPLC method, and metabolic curve was then generated. MPT was tested against Echinococcus granulosus protoscolices in vitro. The result showed that MPT could be metabolized in the three biological media, and to the active compound fenbendazole in liver homogenate, with a metabolic rate of 7.92%. Besides, the prodrug showed a weak activity against E. granulosus protoscolices with a mortality of 45.9%.

A comparative study of 22-channel water-perfusion system and solid-state system with 36-sensors in esophageal manometery.

BACKGROUND: To compare the characteristics between 22-channel water-perfusion manometry (WPM) and solid-state manometry (SSM) with 36 sensors of the pressure measurements, as well as patients' discomfort indices in nose and pharynx, the preparation and operation time of the manometry. METHODS: 12 volunteers were included in the study. Each of the volunteers underwent esophageal manometry by both 22-channel water-perfusion catheter (WPC) and solid-state catheter (SSC) with 36 sensors in random order, and separated by 30 min. The subjects gave a VAS score soon after each test. Non-parametric tests were used to analyze the differences and Bland-Altman plots were used to assess the consistency of the two systems. RESULTS: During the wet swallows, there were significant differences between the two systems in three measurements of location of lower esophageal sphincter (LES) upper margin (Z = -2.11, P = 0.035), LES relax ratio (Z = -2.20, P = 0.028) and IRP4s (Z = -2.05, P = 0.041). During the jelly pocket swallows, LES relax ratio measurements of the two systems showed significant differences (Z = -2.805, P = 0.005). Further Bland-Altman plots analysis presented good agreement between the two systems measurements of location of LES upper margin, LES relax ratio and IRP4s. The discomfort indices of subjects' nasal sensation were higher when inserting the solid-state catheter [5(3.75-5)] than water-perfusion one (2.5(2-4)) (Z = -2.471, P = 0.013), as well as the discomfort indices of pharyngeal sensation (7.5(4.75-9) vs. 4.5(3.75-6.5)), (Z = -2.354, P = 0.019). The preparation time for WPC was 40(39-41) minutes, which was much longer than that for SSC 32.5(31.75-33) minutes, (Z = -3.087, P = 0.002). And the nurses reported it's much easier to insert WPC (Z = -3.126, P = 0.002). CONCLUSIONS: In conclusion, most pressure measurements were consistent between WPM and SSM. Patients tolerated better with WPC, while for operators, the SSC presented more convenient.

Vesicular glutamate transporter-3 contributes to visceral hyperalgesia induced by Trichinella spiralis infection in rats.

BACKGROUND: According to a recent study, vesicular glutamate transporter-3 (VGLUT3) contributes to injury-induced mechanical hyperalgesia in mice. AIMS: The aims of the study were to investigate whether VGLUT3 is involved in visceral pain, and whether transient intestinal infection or acute cold restraint stress (ACRS) affects VGLUT3 expression levels in rats. METHODS: Changes in VGLUT3 and c-Fos proteins were evaluated in rats which received noxious colorectal distension (CRD) stimulation. Transient intestinal infection was effected by oral administration of Trichinella spiralis (T. spiralis) larvae in Brown Norway rats. On the 100th day post-infection (PI), half of the PI-rats and non infected controls were subjected to an ACRS procedure. The visceromotor response to CRD was measured using the abdominal withdrawal reflex (AWR) score. Immunofluorescence and western blot analysis were used to estimate the expression of VGLUT3 in both peripheral and central neurons. RESULTS: Noxious stimulation induced a significant increase in the expression of VGLUT3 in the L6S1 spinal dorsal horn. Compared with the control group, the pain threshold was significantly decreased in the ACRS, PI, and PI + ACRS groups. VGLUT3 expression in the L6S1 dorsal root ganglion (DRG) and spinal neurons were significantly increased in PI and PI + ACRS groups as compared with the control group. CONCLUSIONS: VGLUT3 is involved in conduction of visceral pain sensation and in visceral hyperalgesia induced by Trichinella spiralis infection in rats.

Essential role of mast cells in the visceral hyperalgesia induced by T. spiralis infection and stress in rats.

Mast cells (MCs) deficient rats (Ws/Ws) were used to investigate the roles of MCs in visceral hyperalgesia. Ws/Ws and wild control (+/+) rats were exposed to T. spiralis or submitted to acute cold restraint stress (ACRS). Levels of proteinase-activated receptor 2 (PAR2) and nerve growth factor (NGF) were determined by immunoblots and RT-PCR analysis, and the putative signal pathways including phosphorylated extracellular-regulated kinase (pERK1/2) and transient receptor potential vanilloid receptor 1 (TRPV1) were further identified. Visceral hyperalgesia triggered by ACRS was observed only in +/+ rats. The increased expression of PAR2 and NGF was observed only in +/+ rats induced by T. spiralis and ACRS. The activation of pERK1/2 induced by ACRS occurred only in +/+ rats. However, a significant increase of TRPV1 induced by T. spiralis and ACRS was observed only in +/+ rats. The activation of PAR2 and NGF via both TRPV1 and pERK1/2 signal pathway is dependent on MCs in ACRS-induced visceral hyperalgesia rats.

Heterotopic gastric mucosa in the upper and middle esophagus: 126 cases of gastroscope and clinical characteristics.

BACKGROUND/AIMS: In this retrospective study, we aimed to investigate the prevalence of heterotopic gastric mucosa (HGM) in the upper and middle esophagus, to identify its macroscopic characteristics and evaluate clinical features. METHODOLOGY: One hundred and twenty-six patients (82 males, 44 females; mean age 43.08 ± 12.84 years, range 15-81) with HGM in the upper and middle esophagus diagnosed by gastroscopy and biopsies were admitted to this retrospective study. Disease histories of all patients were carefully inquired, especially the associated complaints including discomfort of throat, heartburn or dysphagia, etc. RESULTS: The prevalence was 0.21%. Patch size ranged between 5-20mm, mean diameter was 7.5 ± 3.7mm; 80 cases appeared as a single patch; 96.83% had the patch in the upper esophagus. Male gender was predominant (male:female ratio, 1.86), but age was not significant. The mean distance from the incisors to the patch was 18.83 ± 2.23cm and 17.20 ± 2.48cm in the male and the female respectively, with a significant difference (t=3.749, p<0.001). In 39 of 126 patients (26 male, 13 female), the esophageal and laryngopharyngeal symptoms were remarkable. Twelve were associated with other diseases of the esophagus. There were no correlations to esophageal symptom, gender, age, location, quantity or diameter. Among the 126 cases, 29 patients were associated with other esophageal diseases. CONCLUSIONS: HGM patches in the esophagus should not be overlooked during endoscopy because they may lead to esophageal symptoms and even important complications in relation to their acid secretions.

[Relationship between intestinal mucosal inflammation and mental disorders in patients with irritable bowel syndrome].

OBJECTIVE: To examine the relationship between inflammation and the comorbidity of mental disorders with irritable bowel syndrome (IBS) by comparing intestinal mucosa inflammatory biomarkers in patients with and without mental disorders. METHODS: A total of 43 consecutive IBS patients fulfilling the Rome III criteria and 15 volunteers serving as controls without digestive symptoms were recruited and interviewed with Composite International Diagnostic Interview (CIDI) by the well-trained staff and thus classified as with or without mental disorders. All subjects underwent colonoscopy and biopsies were acquired from the mucosa of distal ileum and colon. CD3(+) lymphocytes, mast cells, 5-HT positive cells and (indoleamine 2,3-dioxygenase) IDO positive cells were identified immunohistologically in mucosa biopsies in volunteers (n = 13), IBS patients without mental disorder (n = 24) and IBS patients with mental disorder (n = 19). RESULTS: The incidence of mental disorders in IBS patients was significantly higher than that in the volunteers (19/43 vs 2/15, P = 0.012), including 9 patients with anxiety disorders and 8 with mood disorders. (1) The number of mast cells in IBS patients with mental disorder and that in IBS patients without mental disorder has no statistical significance ((16.7 ± 3.6)/HP vs (15.4 ± 3.1)/HP in distal ileum, (12.8 ± 2.2)/HP vs (12.3 ± 2.5)/HP in sigmoid, both P > 0.05). Similar results were seen in 5-HT positive cells ((3.7 ± 0.9)/HP vs (3.4 ± 0.8)/HP in distal ileum, (6.1 ± 1.8)/HP vs (5.2 ± 1.8)/HP in sigmoid, both P > 0.05). In distal ileum, the number of CD3(+) cells in IBS patients with mental disorder has no statistical significance with that in the IBS patients without mental disorder ((62 ± 16)/HP vs (55 ± 22)/HP, P > 0.05). Similar results were seen in IDO positive cells (6(2, 8)/HP vs 2(1, 5)/HP, P > 0.05). (2) The number of IDO positive cells from distal ileum in IBS patients with anxiety disorder was significantly higher than that in the IBS patients without mental disorder (6 (4,8) vs 2 (1,5), P = 0.018). The number of mast cells from distal ileum in the IBS patients with mood disorder were significantly higher than that in those without mental disorders ((18.3 ± 3.2)/HP vs (15.4 ± 3.1)/HP, P = 0.032). CONCLUSIONS: Mental disorders in the IBS patients may be associated with intestinal mucosal inflammation. The activation of IDO may cause the comorbidity of IBS with anxiety disorder while the activation of mast cells probably leads to the comorbidity of IBS with mood disorder.

Differences in cerebral response to esophageal acid stimuli and psychological anticipation in GERD subtypes--an fMRI study.

BACKGROUND: To evaluate whether there are differences in the cerebral response to intraesophageal acid and psychological anticipation stimuli among subtypes of gastroesophageal reflux disease (GERD). METHODS: Thirty nine patients with GERD and 11 healthy controls were enrolled in this study after gastroscopy and 24 hr pH monitoring. GERD subjects were divided into four subgroups: RE (reflux esophagitis), NERD+ (non-erosive reflux disease with excessive acid reflux), NERD-SI+ (normal acid exposure and positive symptom index) and NERD-SI+ (normal acid exposure and negative symptom index, but responded to proton pump inhibitor trial). Cerebral responses to intraesophageal acid and psychological anticipation were evaluated with fMRI. RESULTS: During intraesophageal acid stimulation, the prefrontal cortex (PFC) region was significantly activated in all subgroups of GERD; the insular cortex (IC) region was also activated in RE, NERD+ and NERD-SI- groups; the anterior cingulated cortex (ACC) region was activated only in RE and NERD-SI- groups. The RE subgroup had the shortest peak time in the PFC region after acid was infused, and presented the greatest change in fMRI signals in the PFC and ACC region (P=0.008 and P=0.001, respectively). During psychological anticipation, the PFC was significantly activated in both the control and GERD groups. Activation of the IC region was found in the RE, NERD-SI+ and NERD-SI- subgroups. The ACC was activated only in the NERD-SI+ and NERD-SI- subgroups. In the PFC region, the NERD-SI- subgroup had the shortest onset time (P=0.008) and peak time (P<0.001). Compared with actual acid infusion, ACC in RE and IC in NERD+ were deactivated while additional areas including the IC and ACC were activated in the NERD-SI+ group; and in NERD-SI- group, onset-time and peak time in the PFC and IC areas were obviously shorter in induced anticipation than in actual acid infusion. CONCLUSIONS: The four subgroups of GERD patients and controls showed distinctly different activation patterns and we therefore conclude GERD patients have different patterns of visceral perception and psychological anticipation. Psychological factors play a more important role in NERD-SI+ and NERD-SI- groups than in RE and NERD+ groups.

Synthesis and anti-intestinal nematode activity of variously substituted benzonaphthyridine derivatives.

A series of benzonaphthyridine derivatives bearing the C=N linkage moiety were designed and synthesized. The structures of all the newly synthesized compounds were identified by elemental analysis, 1H-NMR, 13C-NMR and MS. Their anti-intestinal nematode activities against Nippostrongylus brazilliensis were evaluated in vivo by an oral route in male rats. Among these compounds, at concentrations of 10 mg/kg of rat, the compound 7-chloro-2-methoxy-10-(4-(4'-(1H-indol-5'-yl)methylene)aminophenyl)-amino-benzo[b][1,5] naphthyridine (4n) produced the highest activity, with 80.2% deparasitization. These compounds may find usefulness in the discovery and development of new anti-intestinal drugs.

[Research progress in the relationship between TRPV1 and visceral hypersensitivity in functional gastrointestinal diseases].

Transient receptor potential vanilloid 1(TRPV1) is a nonselective cation channel with high permeability for Ca(2+). It may play a role in the development and maintenance of visceral pain and hypersensitivity states, which has generated a major interest in the development of specific vanilloid antagonists. In this review, a summary of the contribution of TRPV1 in the development of visceral hypersensitivity in functional dyspepsia and irritable bowel syndrome is presented with the structure, location, and related molecular mechanisms.

[Effects of infection and stress on transient receptor potential vanilloid receptor 1 and extracellular-regulated kinase in spinal cord of mast cell deficient rats].

OBJECTIVE: To investigate the effects of mast cells (MCs) and the relationship between the signal pathway including transient receptor potential vanilloid receptor 1 (TRPV1) and extracellular-regulated kinase (ERK) and MCs in rat models of visceral hyperalgesia triggered by infection and stress. METHODS: MCs deficient rats (WsRC Ws/Ws, Ws/Ws) and control (WsRC+/+, +/+) rats were exposed to Trichinella spiralis (T.spiralis) post-infection (PI) or submitted to acute cold restraint stress (ACRS). Visceral sensitivity was measured using the abdominal withdrawal reflex (AWR) score. Levels of TRPV1 and phosphorylated ERK1/2 (pERK1/2) proteins in L6S1 spinal cord segments were determined by Western blotting. RESULTS: Compared with control group (3.7±0.09), visceral hyperalgesia was enhanced in PI (2.52±0.13), ACRS (2.28±0.17) and PI+ACRS (2.25±0.12) groups of +/+ rats, P< 0.05. In Ws/Ws rats, compared with control group (3.25±0.20), visceral hyperalgesia was enhanced in PI (2.87± 0.14) and PI+ACRS (2.50±0.27) groups, P< 0.05, but not in ACRS group (2.97±0.22). Compared with control group (0.090±0.009), a significant increase of TRPV1 was observed in PI (0.121±0.012), ACRS (0.122±0.008) and PI+ACRS (0.129±0.008) in spinal cord of +/+ rats, P< 0.05. However, compared with control group (0.106±0.012), a significant increase of TRPV1 was observed in PI (0.140±0.008, P< 0.05) and PI+ACRS (0.156±0.010, P< 0.01) groups but not in ACRS group(0.132±0.014)in spinal cord of Ws/Ws rats. Compared with control group (0.58± 0.03), a significant increase of pERK1/2 was observed in PI (0.72±0.04), ACRS (0.75±0.04) and PI+ACRS (0.78± 0.01) in spinal cord of +/+ rats, P< 0.01. However, compared with control group (0.59±0.04), a significant increase of pERK1/2 was observed in PI (0.72±0.04, P< 0.05) and PI+ACRS (0.74±0.04, P< 0.05) groups but not in ACRS group(0.132±0.014)in spinal cord of Ws/Ws rats. CONCLUSION: The visceral hyperalgesia was enhanced in rats induced by T.spiralis infection and ACRS, however, the increased visceral hyperalgesia in rats induced by ACRS was dependent on MCs. The signal pathway proteins including TRPV1 and pERK1/2 were increased in rats induced by T.spiralis infection and ACRS, but the sensitizing TRPV1 or mobilizing ERK1/2 phosphorylation via a MCs-dependent mechanism plays an important role in ACRS-induced visceral hyperalgesia rats.

[Changes of swallowing function and their significance in Chiari I malformation patients with dysphagia after decompression surgery].

OBJECTIVE: To survey changes of swallowing function and their significance in Chiari I malformation patients with dysphagia after Atlanto-occipital Decompression with Duraplasty by comparing water swallowing test results and other clinical features before and after surgery. METHODS: From January 2007 to July 2010, 126 Chiari I malformation patients were treated in Neurosurgery Department of Peking University Third Hospital. Clinical data were prospectively analyzed. There were 34 cases (26.9%, 34/126) with varying severity of dysphagia. All of those patients underwent Atlanto-occipital Decompression with Duraplasty. Water swallowing tests were performed 1 day before operation and after 7-10 days to assess dysphagia severity. The improvements of other major symptoms and signs after surgery were also compared. RESULTS: Postoperative dysphagia was improved in 23 cases (67.6%, 23/34), and drinking water test score of preoperation was (2.74±1.11). The score was significantly reduced to (1.71±0.91) after the operation (P<0.05). Other major symptoms and signs were analyzed by Fisher's exact test which showed that only neck and shoulder pain (P=0.01) improved significantly, compared with preoperation. CONCLUSION: Indeed part of the Chiari I malformation patients suffer from varying severity of dysphagia. The detailed clinical history collection and physical examination may improve the initial detection rate of dysphagia. Water swallow test is useful to quantify the degree of dysphagia. Atlanto-occipital Decompression with Duraplasty can improve treatment of Chiari I malformation patients with dysphagia. Improvement in treating dysphagia shortly after operation may be an effective index to evaluate the effect of surgery.