Central Effects of Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) on Gastric Motility and Emptying in Rats

Pituitary adenylate cyclase activatingpolypeptide (PACAP) is a new member of thesecretinglucagon-vasoactive intestinal peptide (VIP)peptide family. PACAP is widely distributed not only inthe mammalian brain but also in the gastrointestinal tract.Here, we investigated the effects of central andperipheral administrations of PACAP on gastric motilityand gastric emptying in rats. We found that theintracerebroventricular or intracisternal injection of PACAP increasedgastric motility in a dose-dependent manner. Theintracisternal injection of PACAP delayed gastricemptying. These central effects of PACAP on gastricmotility and emptying were blocked by bilateralvagotomy. In contrast, intravenous administration ofPACAP decreased gastric motility and delayed gastricemptying. The peripheral inhibitory effect wasunaffected by bilateral vagotomy, adrenalectomy,phentolamine, and propranolol. We investigated theeffect of PACAP38 on blood glucose levels (BGL) at thesame doses as those used in the gastric motility andemptying studies in urethane-anesthetized rats. Theintravenous but not intracerebroventricular injection ofPACAP38 (1-8 nmol/rat) produced a significant increasein the BGL. We conclude that PACAP has opposite central and peripheral effects on gastricmotility, ie, central PACAP activates the vagal pathwayin the central nervous system to increase gastricmotility, whereas peripheral PACAP inhibits gastricmotility via an unknown pathway. The delay in gastricemptying after the central administration of PACAP mightbe due to the lack of coordinated gastropyloroduodenalcontraction, whereas that after the peripheral administration might be due to the inhibitionof gastric contraction, and this effect may be relatedto the hyperglycemic action of PACAP.     

幽门螺杆菌、一氧化氮、肥大细胞及其脱颗粒在功能性消化不良各亚型发病中的作用研究

目的探讨幽门螺杆菌(Hp)、一氧化氮(NO)、肥大细胞(MC)及其脱颗粒在功能性消化不良(FD)各亚型发病中的作用。方法按罗马Ⅱ标准选择FD患者35例,取胃窦黏膜若干,行快速尿素酶试验(RUT)、HE染色、14C尿素呼气试验检测Hp;硝酸还原酶比色法测定NO含量;免疫组化法测MC数及其脱颗粒数。结果(1)FD各型间Hp感染率、NO、MC及其脱颗粒数无明显差异。(2)在FD患者,MC与NO呈负相关(r=-0.367,P=0.030<0.05)。结论(1)FD各分型与各指标没有明显关系。(2)FD患者中MC数与NO含量呈负相关,在FD发病中可能有一定意义。     

Measurement of Small Intestinal Permeability Markers, Lactulose, and Mannitol in Serum (Results in Celiac Disease)

To date, tests of small intestinal passivepermeability have involved the ingestion of testmolecules whose permeation is assessed indirectly bymeasuring their urinary recovery. Excretion ratios ofmarker molecules (e.g., lactulose-to-mannitolexcretion ratio, LMER) are useful clinically.Measurement of permeability markers in serum wouldimprove the convenience of the tests. Our aim was toassess small intestinal permeability in celiac patients using serumlactulose and mannitol levels with calculation oflactulose to mannitol serum ratios (LMSR) and to comparethe results with the standard methods using urinary recoveries. Twenty-four newly diagnosed celiacsand 10 control subjects were studied; 10 celiacs wererestudied while established on a gluten-free diet. Testsubjects and patients ingested 10 g lactulose and 2.5 g mannitol in 50 ml water. In 10untreated celiacs and the controls, blood was taken from0 to 120 min and all urine was collected for 6 hr. Theremaining 14 untreated and the 10 treated celiacs had a single serum sample taken 60 min afteringestion of the test solution. At 1 hr after ingestion,the mean mannitol level in normals (0.156 mmol/liter)was significantly higher than in untreated celiacs (0.06 mmol/liter). The 1-hr mean serumlactulose level in normals (0.125 mol/liter) wassignificantly lower than in untreated celiacs (0.56mol/liter). The median 1-hr LMSR in untreatedceliacs was 0.42 compared with 0.039 in normals and 0.08 intreated celiacs. There was a significant correlationbetween LMSR and LMER. Permeability testing using serummeasurements of lactulose and mannitol gave comparable results in celiac patients to the tests usingurinary recovery of the permeability markers and mayprove to be more convenient, especially in pediatricpatients.     

Influence of Type of Dietary Fat (Olive and Sunflower Oil) upon Gastric Acid Secretion and Release of Gastrin, Somatostatin, and Peptide YY in Man

The effects of adaptation to two diets differingin the type of dietary fat on the gastric acid secretoryresponse to food and on the circulating levels ofgastrin, somatostatin and peptide YY (PYY) were examined in humans. The study involved 18cholecystectomized subjects previously submitted to a30-day adaptation period to diets containing olive(group O) or sunflower oil (group S) as the fat source. During the experiments, physiologicalstimulation was achieved by ingestion of 200 ml of oleicacid- (group O) or linoleic acid-enriched (group S)liquid mixed meals. These resulted in an immediate rise in gastric pH. In group S, the return to thepremeal value was completed within 60 min, and a furtherdecline to values significantly lower than the basalones was observed at the end of the study period. In contrast, ingestion of the meal containingolive oil attenuated and prolonged the pH decrease afterthe meal, this being associated with the suppression ofpostprandial gastrin response. Food ingestion induced no significant changes in plasmasomatostatin concentration in either group, and nosignificant differences were revealed between themduring the basal or postprandial situations. Plasma PYYlevels were consistently higher in group O throughoutthe entire study period, although significance wasreached only at resting. In conclusion, our results showthat a 30-day adaptation period to diets containing olive oil as the main source of dietary fatresults, compared with those containing sunflower oil,in an attenuated gastric secretory function in responseto a liquid meal in humans. The effects of olive oil were associated with a suppression of serumgastrin and higher levels of PYY.     

Endotoxin Actions on Myoelectric Activity, Transit, and Neuropeptides in the Gut (Role of Nitric Oxide)

The lipopolysaccharide (endotoxin) ofgram-negative bacteria has systemic effects in animalsand man. Our aim was to investigate the effects of E.coli lipopolysaccharide on motility and transit through the small intestine in rats and to analyzeplasma and tissue concentrations of intestinalneuropeptides. When lipopolysaccharide (20–160g/kg) was administered intravenously, the migratingmyoelectric complex was replaced by spike burstsaccompanied by rapid transit. Tissue concentrations ofsubstance P and neurokinin A decreased, while plasmalevels of calcitonin gene-related peptide increased.N-Nitro-L-arginine, N-L-arginine methyl ester,dexamethasone, or indomethacin prevented these changesin myoelectric activity and tissue contents ofneuropeptides. All of these compounds, exceptindomethacin, prevented the increased rate of transit. Thus,lipopolysaccharide changes motility through the nitricoxide and arachidonic pathways, resulting in rapidtransit through the gut.     

Rabeprazole in Treatment of Acid Peptic Diseases (Results of Three Placebo-Controlled Dose-Response Clinical Trials in Duodenal Ulcer, Gastric Ulcer, and Gastroesophageal Reflux Disease (GERD))

Rabeprazole, a new proton pump inhibitor, wasstudied in patients with acid-pepticrelated diseases(duodenal ulcer, gastric ulcer, GERD) in threeplacebo-controlled, double-blind, randomized clinicaltrials. Men and women over the age of 18 were enrolledif the presence of an active duodenal or gastric ulceror erosive or ulcerative esophagitis was confirmed onupper gastrointestinal endoscopy. Patients were randomly allocated to either placebo orrabeprazole 20 mg or 40 mg in the duodenal and gastriculcer protocols or to placebo or rabeprazole 10 mg, 20mg, or 40 mg in the GERD protocol. All doses ofrabeprazole in all three studies were statisticallysignificantly superior to placebo in healingacid-related lesions. There were no treatmentdifferences between the rabeprazole doses in healingactive peptic lesions. The incidence of positive [¹³C]ureabreath test for H. pylori was 53% in patients withduodenal or gastric ulcers. H. pylori status was noteffected by treatment with rabeprazole.     

Psychosocial Adjustment to Illness Scale (PAIS-SR) in a Norwegian Material of Patients with Functional Dyspepsia,Duodenal Ulcer,and Urinary Bladder Dysfunction: Clinical Validation of the Instrument

Wilhelmsen I, Bakke A, Tangen Haug T, Endresen IM, Berstad A. Psychosocial Adjustment to Illness Scale (PAIS-SR) in a Norwegian material of patients with functional dyspepsia, duodenal ulcer, and urinary bladder dysfunction. Clinical validation of the instrument. Scand J Gastroenterol 1994;29:611-617

Background: There is an increasing interest in the psychosocial impact of a disease, but few instruments available to measure it.

Methods: The internal consistency and construct validity of the Norwegian translation of the Psychosocial Adjustment to Illness Scale (PAIS-SR) was examined in a total of 557 patients.

Results: The seven dimensions of the psychosocial adjustment to medical illness from the original test were represented in the Norwegian translation. Psychologic distress, social environment, and vocational environment explained most of the variance. The instrument had high internal consistency with Cronbach's alpha coefficients of > 0.75 on six of seven subscales. The PAIS-SR differentiated between groups of patients with urologic and upper gastrointestinal disease and seemed to give meaningful and useful clinical data. Patients with functional dyspepsia (n equals; 97) had higher score on psychologic distress than the other groups, whereas patients with duodenal ulcer (n equals; 97) were significantly less affected in their social life than the other patients.

Conclusions: The Norwegian translation of the PAIS-SR had high internal consistency, acceptable construct validity, and good discriminating validity.     

Translation,cross-cultural adaptation,and validation of the Bath Ankylosing Spondylitis Functional Index (BASFI), the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Dougados Functional Index (DFI) in a Spanish speaking population with spondyloarthropathies

OBJECTIVES: The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Functional Index (BASFI) and the Dougados Functional Index (DFI) are the most commonly used instruments to measure disease activity and functioning in ankylosing spondylitis (AS). The aim of this study was to translate, adapt and validate these instruments into the Spanish language. METHODS: The BASDAI, BASFI, and DFI questionnaires were translated into Spanish by three independent bilingual physicians who were familiar with the medical aspects of AS and by one professional translator. Two rheumatologists familiar with instrument validation, and who were aware of the purpose of the study, examined semantic, idiomatic and conceptual issues and produced by consensus unified versions of each instrument. English back-translations from the Spanish were done by a professional translator unaware of the original version. Both English versions were compared, and where needed, modifications to the Spanish versions were made. The Spanish versions were administered to 61 ambulatory patients with AS and to 80 patients with undifferentiated spondyloarthropathy for validation purposes. Reliability and responsiveness were measured in 28 patients participating in a physiotherapy program. RESULTS: Reliability showed an acceptable 24-hour test-retest intraclass correlation coefficient (ICC)--BASFI ICC: 0.68, 95% CI: 0.29-0.85; BASDAI ICC: 0.74, 95% CI: 0.52-0.88 and DFI ICC: 0.87, 95% CI: 0.73-0.94. The construct validity of the instruments was evaluated, and BASDAI was correlated with disease activity measured by the total enthesis count (rs: 0.34); general well being in the last week (rs: 0.7); spinal pain (rs: 0.53) and duration of morning stiffness (rs: 0.64). BASFI correlated with Sch?ber's test (rs: -0.4); occipital-wall distance (rs: 0.38) and thoracic expansion (rs: -0.3). DFI correlated with Sch?ber's test (rs: -0.36); occipital-wall distance (rs: 0.29) and chest expansion (rs: -0.3). The correlation among DFI and BASFI was rs: 0.83. All instruments showed clinical responsiveness in the physiotherapy program (baseline and end of program; mean +/- SD): BASDAI: 6.25 +/- 1.97 and 3.07 +/- 2.04 (p = 0.0001); BASFI: 5.68 +/- 2.29 and 2.88 +/- 1.77 (p = 0.0001); DFI: 16 +/- 7.6 and 8.0 +/- 5.5 (p = 0.001) with effect sizes and standardized effect sizes > 1. CONCLUSIONS: The Mexican Spanish versions of the BASDAI, BASFI, and DFI showed adequate reliability, validity and responsiveness to clinical change. These instruments can be used in the clinical evaluation of Spanish-speaking patients with AS.     

Levels of von Willebrand Factor,Insulin Resistance Syndrome,and a Common vWF Gene Polymorphism in Non-insulin-dependent (Type 2) Diabetes Mellitus

To examine the association between von Willebrand Factor (vWF) concentrations and features of the insulin resistance syndrome, 208 patients with Type 2 (non-insulin-dependent) diabetes (NIDDM) and 80 healthy controls were studied. A restriction fragment length polymorphism in exon 12 of the vWF gene, detected by Aat II endonuclease, was also examined. vWF concentrations were elevated in the patient group (patients 1.28 IU ml⁻¹ vs controls 1.12 IU ml⁻¹, p = 0.003). Genotype frequencies were in Hardy-Weinberg equilibrium and genotype did not relate to vWF levels: means (95 % CI) were AA 1.29 (1.29–1.44) IU ml⁻¹ n = 3; AG 1.28 (1.22–1.26) IU ml⁻¹ n = 48; GG 1.29 (1.25–1.39) IU ml⁻¹ n = 155. vWF correlated with age (r = 0.23 p < 0.0005), duration of diabetes (r = 0.23, p < 0.001), and fibrinogen (r = 0.22, p = 0.002) in the patient group, but was unrelated to blood lipids, HbA_1C, body mass index, glucose, hypertension, and smoking. In a linear regression model, age and insulin remained as independent predictors of vWF levels, explaining 16 % of inter-individual variance in the patient group. In conclusion, these findings show vWF concentrations are elevated in NIDDM and are weakly related to features of the insulin resistance syndrome. No relationship was demonstrated between the gene polymorphism studied and vWF concentrations in this group.     

急性脑血管病人甲状腺素、β_2微球蛋白的测定及分析

本文报告80例急性脑血管病与对照组比较，T3明显降低，T4无改变，β2微球蛋白明显提高。指出急性脑血管病甲状腺素改变可能与脑水肿有关，而β2微球蛋白升高提示免疫失调在急性脑血管病发病中有一定意义。     

不同类型冠心病患者血尿酸、纤维蛋白原、低密度脂蛋白和脂蛋白(a)浓度的变化

目的 研究不同类型冠心病患者血尿酸、纤维蛋白原、低密度脂蛋白和脂蛋白(a)浓度的变化及其与冠状动脉病变程度的关系.方法 185例患者包括107例急性冠状动脉综合征患者、30例冠状动脉痉挛患者及48例稳定型心绞痛患者,以31例非冠心病者为对照组.测定血清尿酸、纤维蛋白原、低密度脂蛋白和脂蛋白(a)浓度,冠状动脉病变严重程度用常规冠状动脉造影后计算Gensini积分与病变支数来估计.结果 急性冠状动脉综合征组、冠状动脉痉挛组和稳定型心绞痛组中男性患者血尿酸浓度高于对照组.急性冠状动脉综合征组和稳定型心绞痛组中女性患者血尿酸浓度高于对照组(P<0.05);急性冠状动脉综合征组血纤维蛋白原浓度高于对照组和稳定型心绞痛组(P<0.05).尿酸、纤维蛋白原和低密度脂蛋白与冠状动脉积分显著相关,尿酸、纤维蛋白原与冠状动脉病变支数显著相关.结论 各型冠心病及其严重程度与血尿酸、纤维蛋白原浓度升高有关,血低密度脂蛋白与冠状动脉积分有关.     

The Detection of Campylobacter pylori (Cp) in Gastro-Duodenal Disease: The Efficacy of the Rapid Urease (RU) Test and Relationship between Endoscopic Findings,Histological Gastritis and Presence of Cp

Abstract: In the comparison of bacteriological and histological methods, the rapid urease (RU) test was considered a specific (100%) method for detection of Campylobacter Pylori (Cp), by which the presence of Cp can be rapidly judged (more than 90% in 20 min.). For an accurate and reliable diagnosis, other methods should be used concurrently, because the sensitivity of this test was inferior to bacteriological methods by 10 to 20%. In the histological study, polymorphonuclear leukocyte infiltration in the antral mucosa clearly reflected Cp infection. This pathological change responded well to antibacterial therapy. Of some endoscopic findings in the gastric antrum, verrucous change was considered to have a relatively close association with Cp infection. However, about 30% of Cp-present cases had endoscopically no abnormal appearance in the gastric antrum.     

Expression of Interleukin (IL)-10, IL-17A and IL-22 in Serum and Sputum of Stable Chronic Obstructive Pulmonary Disease Patients

Abstract

Interleukin (IL)-17A, IL-22 and IL-10 have been implicated in the development of chronic obstructive pulmonary disease (COPD), but their expression in COPD is uncertain. Here we investigate the expression of IL-17A, IL-22 and IL-10 in the serum and sputum of COPD patients. Blood samples and induced sputum samples were collected from 94 patients with COPD, 23 healthy smokers, and 22 healthy control non-smokers. IL-17A, IL-22 and IL-10 were measured by enzyme-linked immunosorbent assay (ELISA). We found that: 1) serum and sputum IL-17A were higher in COPD compared to healthy smokers and non-smokers; 2) serum IL-17A increased with COPD stages, it was inversely correlated with percentage of forced expiratory volume in the first second (FEV₁%) reference and positively correlated with C-reactive protein (CRP), Sputum IL-17A levels in the severe COPD patients were positively correlated with sputum neutrophils, and reversely correlated with sputum macraphages (p < 0.01); 3) serum and sputum IL-22 were significantly higher in COPD and healthy smokers than those in the non-smoker group, sputum IL-22 was similar in severe COPD (stage III and IV), which were higher than those in the other groups (p < 0.05); and, 4) serum and sputum IL-10 were similiar in COPD and healthy smokers, which were decreased compared to non-smokers. These data suggest that the increased level of IL-17A in serum and sputum plays important roles in the pathogenesis of COPD. The increased sputum IL-22 might also play important roles in the pathogenesis of COPD, while IL-10 secretion might be not only affected by COPD but also by cigarette smoke.     

Influence of Radiofrequency Energy Delivery at the Gastroesophageal Junction (the Stretta Procedure) on Symptoms,Acid Exposure,and Esophageal Sensitivity to Acid Perfusion in Gastroesophagal Reflux Disease

Several studies have demonstrated that radiofrequency energy delivery at the gastroesophageal junction (the Stretta procedure) induces symptom relief in gastroesophageal reflux disease (GERD), although improvement of acid exposure on pH monitoring was usually limited. A role for decreased esophageal sensitivity has been suggested. Our aim was to evaluate the influence of Stretta on symptoms, acid exposure, and sensitivity to esophageal acid perfusion in GERD. Thirteen patients with established proton pump inhibitor (PPI)-dependent GERD (three males; mean age, 51±10 years) participated in the study. Before and 6 months after the procedure symptom score, pH monitoring and Bernstein acid perfusion test were performed. The latter was done by infusing HCl (pH 0.1) at a rate of 6 ml/min 15 cm proximal to the gastroesophageal junction for a maximum of 30 min or until the patients experienced heartburn. Results were compared by Student’s t-test. Stretta procedure time was 51±4 min and no complications occurred. After 6 months, the symptom score was significantly improved (12.5±2.0 to 7.5±2.1; P<0.05), seven patients no longer needed daily PPI, and acid exposure was significantly decreased (11.6%±1.6% to 8.5%±1.8% of time pH<4; P<0.05). The time needed to induce heartburn during acid perfusion decreased from 9.5±2.3 to 18.1±3.4 min (P=0.01), and five patients became insensitive to 30-min acid perfusion, versus none at baseline (P=0.04). In conclusion, the Stretta procedure induces subjective improvement of GERD symptoms and decreases esophageal acid exposure. In addition, esophageal acid sensitivity is decreased 6 months after the Stretta procedure. The mechanism underlying this finding and its relevance to symptom control require further studies.     

Evolution of Surface Topography and Microstructure in Laser Polishing of Cold Work Steel 1.2379 (AISI D2) Using Quadratic,Top-Hat Shaped Intensity Distributions

Within the scope of this study, basic experimental research was carried out on macro-laser polishing of tool steel 1.2379 (D2) using a square intensity distribution and continuous wave laser radiation. The influence of the individual process parameters on surface topography was analyzed by a systematic investigation of a wide range of process parameters for two different, square laser beam diameters. Contrary to a typical laser polishing approach, it was shown that short interaction times (high scanning velocity and small laser beam dimensions) are required to reduce both micro-roughness and meso-roughness. A significant reduction of surface roughness of approx. 46% was achieved from Ra_ini = 0.33 ± 0.026 µm to Ra_min = 0.163 ± 0.018 µm using a focused square laser beam with an edge length of d_L,E = 100 µm at a scanning velocity of v_scan = 200 mm/s, a laser power P_L = 60 W and n = 2 passes. However, characteristic surface features occur during laser polishing and are a direct consequence of the laser polishing process. Martensite needles in the micro-roughness region, undercuts in the meso-roughness region, and surface waviness in the macro-roughness region can dominate different regions of the resulting surface roughness spectrum. In terms of mechanical properties, average surface hardness was determined by hundreds of nano-indentation measurements and was approx. 390 ± 21 HV0.1 and particularly homogeneous over the whole laser polished surface.     

Coronary calcification, homocysteine, C-reactive protein and the metabolic syndrome in Type 2 diabetes: the Prospective Evaluation of Diabetic Ischaemic Heart Disease by Coronary Tomography (PREDICT) Study.

AIMS: The PREDICT Study aims to determine: (i) the association between cardiovascular risk factors and coronary artery calcification score (CACS) obtained by electron beam tomography and (ii) the predictive value of CACS for coronary heart disease (CHD) events in Type 2 diabetes. METHODS: Having previously reported relationships between CACS and conventional risk factors, we have now studied the novel risk factors, plasma high-sensitivity C-reactive protein (CRP) and homocysteine, insulin resistance, serum apoprotein A1 and B concentrations, the serum triglyceride/high-density lipoprotein cholesterol ratio and metabolic syndrome (International Diabetes Federation definition) in 573 subjects of the PREDICT Type 2 diabetes cohort. RESULTS: In univariate analyses, the only significant positive novel correlate of CACS was homocysteine (P = 0.0004). CRP was increased in those with detectable calcification, but decreased with increasing calcification score (P = 0.006). In a multivariate model that included all significant univariate correlates, CACS was independently associated with age (P < 0.0001), waist-hip ratio (P < 0.02), male gender (P < 0.05) and duration of diabetes (P < 0.05), but the association with homocysteine was no longer significant. The negative association between CACS and CRP remained in multivariate analysis, and was independent of statin use. CONCLUSIONS: Age was the major factor influencing CACS in Type 2 diabetes, with weaker contributions from waist hip-ratio and duration of diabetes. Other novel cardiovascular risk factors appear to have little positive effect.     

Measurement of indicator genes using global complementary DNA (cDNA) amplification,by polyadenylic acid reverse transcriptase polymerase chain reaction (poly A RT-PCR): A feasibility study using paired samples from tissue and ductal juice in patients undergoing pancreatoduodenectomy

Objectives

The aim of this study is to compare gene expression profiles in RNA isolated from pancreatic ductal juice with the RNA expression profiles of the same genes from matched intra-operative tissue samples from pancreatic tumours.