Integrated Relaxation Pressure and Its Diagnostic Ability May Vary According to the Conditions Used for HREM Recording.

Integrated Residual Pressure (IRP) measured under conditions alternative to supine single swallows may provide clinically useful information regarding EGJ relaxation. This study aimed to compare IRP values obtained under different situations and explore their potential clinical utility. We analyzed and compared the values of IRP obtained from healthy volunteers and patients with suspected achalasia during supine single swallows (Ssup-IRP), sitting single swallows (Ssit-IRP), supine multiple rapid swallows (Msup-IRP), and sitting multiple rapid swallows (Msit-IRP). We analyzed the HREM recordings of 40 healthy volunteers and 53 patients with suspected achalasia. The four metrics were significantly different from each other in healthy volunteers (Ssup-IRP > Msup-IRP > Ssit-IRP > Msit-IRP) and their corresponding 95th percentiles were substantially distinct (Ssup-IRP: 25.3 mmHg, Ssit-IRP: 20.9 mmHg, Msup-IRP: 15.9 mmHg, and Msit-IRP: 11.9 mm Hg, respectively). Complete agreement among the four metrics in predicting abnormal IRP was found in 39 of the 47 patients with suspected achalasia who completed the protocol. Optimal cutoffs derived from ROC curve analysis demonstrated ≥ 0.95 specificities for detection of impaired EGJ relaxation among patients with suspected achalasia. Among the eight patients with suspected achalasia with normal Ssup-IRP, five demonstrated abnormal Msit-IRP and four abnormal Ssit-IRP. Significant differences of IRP exist depending on the measurement situation, indicating that correct interpretation of IRP values requires specific cutoffs for each situation.The sensitivities of Ssit-IRP and Msit-IRP in detecting defective EGJ relaxation appear to be slightly higher than that of Ssup-IRP.

Prevalence of Helicobacter pylori genotypes: cagA, vacA (m1), vacA (s1), babA2, dupA, iceA1, oipA and their association with gastrointestinal diseases. A cross-sectional study in Quito-Ecuador.

BACKGROUND: The most prevalent stomach infection in the world is caused by Helicobacter pylori (H. pylori). Several pathogenicity genes, including cagA, vacA, babA2, dupA, iceA, and oipA, are associated with an increased risk of gastrointestinal disease such as peptic ulcer and stomach cancer. This research aims to determine the prevalence of different H. pylori genotypes and correlate their risk in the development of gastrointestinal diseases in the Ecuadorian population. METHODS: A cross-sectional research of 225 patients at the Calderón Hospital in Quito, Ecuador, was conducted. End point PCRs were run to determine the presence of 16S rRNA, cagA, vacA (m1), vacA (s1), babA2, dupA, iceA1, and oipA virulence genes. Chi-square test, odds ratios (OR) and 95% confidence intervals (CI) were utilized for the statistical analysis. RESULTS: H. pylori infection was present in 62.7% of people. Peptic ulcers were seen in 22.2% and malignant lesions in 3.6% of patients. Genes oipA (93.6%), vacA (s1) (70.9%), and babA2 (70.2%) were the most prevalent. cagA/vacA (s1m1) and cagA/oipA (s1m1) combinations were found in 31.2% and 22.7% of the cases, respectively. Acute inflammation has a significant correlation with the genes cagA (OR = 4.96 95% CI: 1.1-22.41), babA2 (OR = 2.78 95% CI: 1.06-7.3), and the cagA/oipA combination (OR = 4.78, 95% CI: 1.06-21.62). Follicular hyperplasia was associated with iceA1 (OR = 3.13; 95% CI: 1.2-8.16), babA2 (OR = 2.56; 95% CI: 1.14-5.77), cagA (OR = 2.19; 95% CI: 1.06-4.52), and the cagA/oipA combination (OR = 2.32, 95% CI: 1.12-4.84). The vacA (m1) and vacA (s1m1) genes were associated with gastric intestinal metaplasia (OR = 2.71 95% CI: 1.17-6.29) (OR = 2.33 95% CI: 1.03-5.24). Finally, we showed that cagA/vacA (s1m1) gene combination increased the risk of duodenal ulcer development (OR = 2.89, 95% CI 1.10-7.58). CONCLUSION: This study makes a significant contribution by offering genotypic information regarding H. pylori infection. The presence of several H. pylori genes was associated with the onset of gastrointestinal illness in the Ecuadorian population.

Salivary Hemoglobin Protects against Erosive Tooth Wear in Gastric Reflux Patients.

OBJECTIVE: Saliva is the most important biological factor to protect against erosive tooth wear (ETW). Gastroesophageal reflux disease (GERD) patients have an increased risk of ETW due to the frequent presence of intrinsic acids in the oral cavity. Remarkably, not all GERD patients suffer from ETW, which might be due to differences in the composition of the saliva. METHODS: This study compared the proteomic profile of saliva in patients (1) with GERD and ETW (basic erosive wear examination, BEWE, score ≥9; GE group) and (2) with GERD without ETW (BEWE = 0; GNE group) using shotgun label-free quantitative proteomic analysis nLC-ESI-MS/MS. The ability of hemoglobin (Hb) to protect against initial enamel erosion caused by a daily 10-s immersion of enamel specimens in 0.01 M HCl (pH 2.3) for 3 days was evaluated in vitro for proof of concept. Surface hardness change was used as response variable. RESULTS: The differential expression of Hb subunits was significantly increased in the GNE group versus the GE group, in particular the Hb α-subunit that showed a >22-fold increase. Expressions of serum albumin (4.5-fold) and isoforms of cytoskeletal keratin type II (>3-fold) were also increased in the GNE group. Proteinase inhibitors, such as α1-antitrypsin and α2-macroglobulin, were only identified in the GNE group. In vitro, Hb (1.0 and 4.0 mg/mL) significantly reduced initial enamel erosion compared to a negative control after 3 days. CONCLUSIONS: Our results indicate that many proteins, with special emphasis on Hb, may be involved in the resistance of GERD patients to the occurrence of ETW. These proteins may be candidates for inclusion in dental products to protect against ETW.

Distal contractile integral measurement and vascular compression in the esophagus: a problem unsolved?

BACKGROUND: Distal contractile integral (DCI) is influenced by factors other than esophageal smooth muscle contractility, such as intrabolus pressure and vascular and respiratory movements' artifacts. We aimed to determine the size of the contribution of pressures generated by vascular compression on the esophagus to the DCI measured in HRM recordings in symptomatic patients. METHODS: HRM manometry recordings obtained from 383 subjects referred to the GI motility laboratory at a tertiary center (2012-2016) were evaluated by visual inspection for evidence of strong vascular compression (SVC) of the esophagus. Clinical, demographic, manometric, and serologic data for Chagas disease were obtained. Subjects were classified, respectively, as asymptomatics (ASYM) or symptomatics (SYMP). DCI and SVC-DCI were measured, and the SVC-DCI/DCI ratio was expressed as a percentage and the difference between DCI and SVC-DCI (neat-DCI) was calculated. DCI, SVC-DCI, SVC-DCI/DCI % and neat-DCI from SYMP and ASYM were compared. RESULTS: SVC was conspicuous in 42 of 383 subjects (11%). In 33 subjects, SVC was detected only in supine position. SVC was localized in middle esophagus in 21 subjects (50%), in distal esophagus in 12 subjects (29%) and in both regions in 9 subjects (21%). In 9 subjects, SVC vanished from the swallowing window analysis (21%). CONCLUSIONS: SVC is a common finding in esophageal HRM study, particularly in the supine position. Occasionally, its contribution to DCI value is sufficiently great to masquerade esophageal hypocontractility. Different manometric protocols may be required in patients with SVC.

Inspiratory muscle training improves antireflux barrier in GERD patients.

The crural diaphragm (CD) is an essential component of the esophagogastric junction (EGJ), and inspiratory exercises may modify its function. This study's goal is to verify if inspiratory muscle training (IMT) improves EGJ motility and gastroesophageal reflux (GER). Twelve GER disease [GERD; 7 males, 20-47 yr, 9 esophagitis, and 3 nonerosive reflex disease (NERD)] and 7 healthy volunteers (3 males, 20-41 yr) performed esophageal pH monitoring, manometry, and heart rate variability (HRV) studies. A 6-cm sleeve catheter measured average EGJ pressure during resting, peak inspiratory EGJ pressures during sinus arrhythmia maneuver (SAM) and inhalations under 17-, 35-, and 70-cmH2O loads (TH maneuvers), and along 1 h after a meal. GERD patients entered a 5-days-a-week IMT program. One author scored heartburn and regurgitation before and after IMT. IMT increased average EGJ pressure (19.7 ± 2.4 vs. 29.5 ± 2.1 mmHg; P < 0.001) and inspiratory EGJ pressure during SAM (89.6 ± 7.6 vs. 125.6 ± 13.3 mmHg; P = 0.001) and during TH maneuvers. The EGJ-pressure gain across 35- and 70-cmH2O loads was lower for GERD volunteers. The number and cumulative duration of the transient lower esophageal sphincter relaxations decreased after IMT. Proximal progression of GER decreased after IMT but not the distal acid exposure. Low-frequency power increased after IMT and the higher its increment the lower the increment of supine acid exposure. IMT decreased heartburn and regurgitation scores. In conclusion, IMT improved EGJ pressure, reduced GER proximal progression, and reduced GERD symptoms. Some GERD patients have a CD failure, and IMT may prove beneficial as a GERD add-on treatment.

Pharmacomagnetography assessment of the prokinetic effect on metronidazole absorption.

OBJECTIVES: This study aimed to evaluate the effects of prucalopride, a prokinetic agent that acts as a potent serotonin agonist of 5-HT4 receptors, on gastric emptying and small bowel transit and assess its impact on the absorption of metronidazole. METHODS: Six healthy volunteers, three men and three women, aged between 20 and 27 years, with a body weight ranging from 50 to 80 kg, were enrolled in this study. The pharmacokinetics and gastrointestinal transit parameters were evaluated simultaneously through pharmacomagnetography assessment, combining alternating current biosusceptometry and blood analysis. KEY FINDINGS: The results showed that prucalopride enhances gastric emptying and small bowel transit when administered orally and significantly impacts the rate of metronidazole absorption, leading to enhanced bioavailability and rapid therapeutic response. CONCLUSION: Pharmacomagnetography assessment allows simultaneous tracking of transit by images and is a valuable method for analysing drug absorption using multiple instruments.

Proteomic analysis of stimulated saliva in gastroesophageal reflux disease patients with and without erosive tooth wear: Observational study.

OBJECTIVE: To evaluate the difference in the proteomic profile of stimulated saliva in patients with gastroesophageal reflux disease (GERD) with (GE) and without (GNE) erosive tooth wear (ETW), regarding both human and bacterial proteins. METHODS: Stimulated saliva (SS) was collected from 16 patients (8/group). Samples were centrifuged at 4.500 g for 15 min under refrigeration to remove all debris. The supernatant from each saliva sample was taken and frozen at -80 °C. After extracting the proteins, they were submitted to reverse phase liquid chromatography and mass spectrometry (nLC-ESI-MS/MS). Label-free proteomic quantification was performed using Protein Lynx Global Service (PLGS) software (p < 0.05) for human and bacterial proteins. RESULTS: In total, 67 human proteins were common for GNE and GE groups. GNE group presented, compared to GE group, increase in proteins that confer antimicrobial and acid resistant properties, such as cystatins, histatin and immunoglobulins. However, GNE group had a marked decrease in subunits of hemoglobin (α, ß and delta). Regarding bacterial proteins, for SS, 7 and 10 unique proteins were identified in the GE and GNE groups, respectively. They are related to protein synthesis and energy metabolism and interact with human proteins typically found in saliva and supramolecular complexes of the acquired pellicle. CONCLUSIONS: Our data indicate that the stimulation of the salivary flow increases acid resistant and antimicrobial proteins in saliva, which might protect against ETW. CLINICAL SIGNIFICANCE: This pioneer study showed important differences in the human and bacterial proteome of SS in patients with GERD with or without ETW.

The essential oil of Eucalyptus tereticornis and its constituents, α- and ß-pinene, show accelerative properties on rat gastrointestinal transit.

The essential oil of Eucalyptus tereticornis (EOET) has pharmacological activities but their effects on the gastrointestinal tract are yet unknown. It possesses α- and ß-pinene as minor constituents, isomers largely used as food or drink additives. In this work, we studied their actions on gut motility. After feeding with a liquid test meal, conscious rats received perorally EOET, α-, or ß-pinene, and the fractional dye retention was determined. EOET and its constituents decreased the gastric retention. In anesthetized rats, pinenes increased gastric tonus, while enhancing the meal progression in the small intestine of conscious rats. Both α- and ß-pinene contracted gastric strips IN VITRO but relaxed the duodenum. Conversely, EOET relaxed both the gastric and duodenal strips. In conclusion, EOET accelerates the gastric emptying of liquid, and part of its action is attributed to the contrasting effects induced by α- and ß-pinene on the gut.

Role of cholecystokinin and oxytocin in slower gastric emptying induced by physical exercise in rats.

Vigorous exercise can induce gastrointestinal disorders such decreased gastric emptying pace, while low-intensity exercise can accelerate gastric motility. However, the mechanisms of these effects are still unknown. We investigated the possible neurohumoral mechanisms involved in these phenomena. In sedentary (Sed) and acute exercise (Ex) groups of rats, we assessed the activation of c-Fos in NTS and DVMN and the plasma levels of CCK and OXT. Separate groups received pretreatment with the oxytocin antagonist atosiban (AT), the cholecystokinin antagonist devazepide (DVZ), or the TRPV1 receptor inhibitor capsazepine (CAPZ). AT, DVZ and CAPZ treatments prevented (p<0.05) slower gastric emptying induced by acute exercise. The gene expression of OXT decreased (P<0.05) while that of CCK increased (P<0.05) in the gastric fundus and pylorus of the Ex group, while the plasma levels of OXT rose (p<0.05) and of CCK declined (p<5.05). We also observed activation (p<0.05) of c-Fos-sensitive neurons in the NTS and DVMN of exercised rats. In conclusion, acute exercise slowed gastric emptying by the vagal afferent pathway, which involved activation of CCK1/OXT/TRPV1 sensitivity.

High intestinal hydrogen production in runners after intake of fructose solution.

Fructose intake is associated with increased consumption of processed foods, specifically in the context of nutritional supplements. To assess gastrointestinal symptoms and hydrogen production after the ingestion of a fructose solution in runners, healthy and sick persons. Hydrogen test (H2 test) was performed after the intake a solution with 50 g fructose along with the application of a questionnaire to evaluate the gastrointestinal symptoms during the H2 test in three groups: Athletes group (AG); control group (CG) with healthy subjects; and non-alcoholic fatty liver disease group (NAFLDG). Statistical analysis was performed with analysis of variance at a p < 0.05 significance level. The AG was the largest H2 producer followed by the CG with significant difference between the AG and NAFLDG (p ≤ 0.05). Most participants remained asymptomatic, but the strongest correlation was the symptom of bloating GC (R = 0.625), eructation in NAFLD (R = 0.481) and diarrhea in CG (R = 0.345) and AG (R = 0.338) The result of the present study suggests the production of hydrogen by the colon following the administration of fructose is higher in athletes compared with healthy individuals and persons with NAFLD, showing that fructose intake may be an interesting point of dietary management, especially in elite professionals.

Clinical feasibility of Açai (Euterpe olerácea) pulp as an oral contrast agent for magnetic resonance cholangiopancreatography.

BACKGROUND: We evaluate the effectiveness of the Amazonian fruit pulp from Euterpe olerácea (popularly named Açaí) as a negative oral contrast agent applied to clinical routine. The use of such contrasts is particularly important in magnetic resonance cholangiopancreatography (MRCP) to reduce overlapping. MATERIALS AND METHODS: We administered Açaí pulp to 5 nonsymptomatic subjects and 35 patients submitted to unspecific abdominal MR imaging, intending to set up optimal protocol. In 8 MRCP examinations, contrast and image effects were assessed and graded blindly by 2 independent radiologists. Quantitative analysis was performed by Wilcoxon test as to verify the potential of the Açaí to eliminate overlap signal over the pancreaticobiliary tract. Adverse effects and subject tolerance were also addressed. RESULTS: The Açaí pulp elicited a local brightness decrease in T2-weighted images. The depiction of gallbladder, common bile duct, ampulla of Vater, and pancreatic duct was markedly improved after Açaí ingestion because of the suppression of the overlapping from bowel loops and gastric content (P < 0.01). All patients considered Açaí palatable, and no side effect was registered. CONCLUSIONS: The Açaí pulp can be used routinely in MRCP studies as a natural, safe, and inexpensive negative oral contrast agent with high efficacy and patient acceptance.

Impact of depressive symptoms on visceral sensitivity among patients with different subtypes of irritable bowel syndrome.

The etiology of irritable bowel syndrome (IBS) is complex and multifaceted. Psychosocial factors play a role in such a process. Several reports suggest that IBS patients have increased psychopathology scores as compared with population controls. The influence of depressive symptoms on rectal sensitivity thresholds vary across different studies. The influence of predominant bowel habits on rectal sensitivity thresholds as determined by barostat-based investigations is not well established. The present report aimed to investigate the influence of depressive symptoms on rectal sensitivity in different subtypes of IBS patients (diarrhea/constipation-predominant vs. alternating subtypes). Depressive symptoms correlated well with first pain sensitivity threshold in alternating patients (n = 8; [rho] = -0.77; p = 0.02) but not in diarrhea/constipation predominant symptoms (n = 11; [rho] = -0.44; p = 0.27). These data suggest that depressive symptoms might impact pain thresholds differently according to the subtype of IBS.

Association between Helicobacter pylori genotypes and gastric disorders in relation to the cag pathogenicity island.

Helicobacter pylori is a bacterium associated with upper gastrointestinal diseases in humans. However, only a small proportion of infected people become sick. Although several studies have tried to establish an association between known virulence markers and clinical outcomes, in many cases the results have been conflicting. The aim of this study was to investigate the importance of virulence markers to predict clinical outcome in Brazil. Mixed infections by genetically unrelated strains detected by vacA genotyping were found in 18% of the patients. The cagA and cagE genes and the vacAs1 genotype were associated with the development of peptic ulcer disease (PUD). The cagAvacAs1m1 genotype was associated with PUD and duodenal ulcer (DU). Conversely, jhp947 was not associated with DU or PUD, indicating that this gene is not a universal virulence marker. These results also show that a high proportion of the patients were simultaneously infected by cag-positive and cag-negative H. pylori types. This finding suggests the existence of a dynamic equilibrium between the loss and gain of the cag pathogenicity island, probably depending on the physiologic conditions of the patient's stomach. To the best of our knowledge, this is the first study that has documented this finding in Brazil.

Prevalence of Helicobacter pylori cagA, iceA and babA2 alleles in Brazilian patients with upper gastrointestinal diseases.

Helicobacter pylori is an important human pathogen associated with gastrointestinal diseases such as gastritis, gastric and duodenal ulcer (peptic ulcer disease, PUD), and gastric cancer. A number of pathogenic factors have been described for this bacterium, and some of them have been proposed as markers for the prediction of the clinical outcome. However, with the exception of the cag and vacA status, there is no universal consensus regarding the importance of the other virulence factors. Therefore, the aim of this study was to investigate the status of H. pylori strains regarding the babA and iceA alleles, as well as the cagA genotype, to reveal any association between these genotypes and clinical outcomes in Brazilian patients. The great majority (92.6%) of the strains were typed as iceA1, while 40.4% were found to possess the babA2 allele. The cagA gene was detected in 73.4% of the strains. The iceA2 and cagA genotypes were associated with PUD, while iceA1 was negatively correlated with PUD. However, considering the high percentage of strains typed as iceA1, these associations must be treated with caution. No clinical entity was associated with the babA2 allele. These results suggest that iceA1 is not a good marker for the diseases associated with H. pylori infection in Brazil. Further studies are needed in order to elucidate the relevance of the babA status, because other studies performed in Brazil have associated the babA2 allele with clinical outcomes. These results also indicate the existence of regional differences in the H. pylori genotypes and their association with clinical outcomes.

[Features of Chagas' disease patients with emphasis on digestive form, in a tertiary hospital of Ribeirão Preto, SP]. / O perfil dos portadores de doença de Chagas, com ênfase na forma digestiva, em hospital terciário de Ribeirão Preto, SP.

In order to characterize the demographic and clinical profile of patients with digestive manifestations of Chagas' disease, the medical records were reviewed of patients (n = 377) currently attended at Hospital das Clinicas da Faculdade de Medicina de Ribeirão Preto with positive serologic reaction for Chagas' disease and admitted from January 2002 to March 2003. Median age was 67 years and 210 (56%) were women. Megaesophagus and/or megacolon were present in 135 patients, 59% of these had cardiopathy. For 49% of patients with digestive disease, at least two medical prescriptions of medicines for the treatment of cardiovascular diseases were found. In 66 patients, chronic comorbidities were detected. The population with digestive manifestation of Chagas' disease referred to HCFMRP is mostly geriatric, with an elevated frequency of cardiopathy, which may indicate a high risk for surgical approach to the treatment of chagasic megaesophagus and megacolon.

Subtotal nephrectomy inhibits the gastric emptying of liquid in awake rats.

Homeostasis of blood volume (BV) is attained through a functional interaction between the cardiovascular and renal systems. The gastrointestinal tract also adjusts its permeability and motor behavior after acute BV imbalances. We evaluated the effect of progressive nephron loss on gut motility. Male Wistar rats were subjected or not (sham) to 5/6 partial nephrectomy (PNX) in two steps (0 and 7th day). After further 3, 7, or 14 days, PNX and sham operation (control) rats were instrumented to monitor mean arterial pressure (MAP), central venous pressure (CVP), heart rate (HR), and blood collection for biochemical analysis. The next day, they were gavage fed with a liquid test meal (phenol red in glucose solution), and fractional dye recovery determined 10, 20, or 30 min later. The effect of nonhypotensive hypovolemia and the role of neuroautonomic pathways on PNX-induced gastric emptying (GE) delay were also evaluated. Compared with the sham-operated group, PNX rats exhibited higher (P < 0.05) MAP and CVP values as well as increased values of gastric dye recovery, phenomenon proportional to the BV values. Gastric retention was prevented by prior hypovolemia, bilateral subdiaphragmatic vagotomy, coelic ganglionectomy + splanchnicectomy, guanethidine, or atropine pretreatment. PNX also inhibited (P < 0.05) the marker's progression through the small intestine. In anesthetized rats, PNX increased (P < 0.05) gastric volume, measured by a balloon catheter in a barostat system. In conclusion, the progressive loss of kidney function delayed the GE rate, which may contribute to gut dysmotility complaints associated with severe renal failure.

[Nutritional status and dietary assessment of patients with gastrectomy]. / Estado nutricional e avaliação dietética de pacientes gastrectomizados.

BACKGROUND: Nutrition is a crucial factor in gastric resection surgery and the most suitable alimentary canal reconstruction method must be considered in order to reduce the risk of malnutrition. The cause of postgastrectomy malnutrition has not been clearly determined, but the mechanisms behind malnutrition are evidently multifactorial. AIM: To evaluate the nutritional status of patients who underwent different reconstructive procedures after total or subtotal gastrectomy. PATIENTS AND METHODS: Fifty patients who have undergone gastrectomy for 0.5-39 years were assessed. The surgical procedures used were Billroth I in 7, Billroth II in 26, Henley in 3 and Roux-en-Y in 14 of the patients. Twenty one of them have followed gastrectomy for cancer. The nutritional status was evaluated by subjective global assessment, dietary recall and anthropometry. RESULTS: According to subjective global assessment, 6 of 50 patients were mild malnourished. The mean body mass index was 22 4.75 kg/m2, the average daily calorie intake was 1624 477 Kcal. Of the patients operated for cancer, those who underwent subtotal gastrectomy followed by Roux-en-Y presented higher body mass index. No relationship between the period of time since surgery with body mass index or with calorie intake was found. CONCLUSIONS: Among patients operated for cancer, subtotal gastrectomy with Roux-en-Y reconstruction is associated with better nutritional status. Factors other than low calorie intake are the cause of weight loss in patients with gastrectomy.

Development of an AMR-ACB array for gastrointestinal motility studies.

The association between anisotropic magnetoresistive (AMR) sensor and AC biosusceptometry (ACB) to evaluate gastrointestinal motility is presented. The AMR-ACB system was successfully characterized in a bench-top study, and in vivo results were compared with those obtained by means of simultaneous manometry. Both AMR-ACB and manometry techniques presented high temporal cross correlation between the two periodicals signals . The contraction frequencies using AMR-ACB were 73.9 ± 7.6 mHz and using manometry were 73.8 ± 7.9 mHz during the baseline . The amplitude of contraction using AMR-ACB was 396 ± 108 µT·s and using manometry were 540 ± 198 mmHg·s during the baseline. The amplitudes of signals for AMR-ACB and manometric recordings were similarly increased to 86.4% and 89.3% by neostigmine, and also decreased to 27.2% and 21.4% by hyoscine butylbromide in all animals, respectively. The AMR-ACB array is nonexpensive, portable, and has high-spatiotemporal resolution to provide helpful information about gastrointestinal tract.

Inhibitory effect of sildenafil on rat duodenal contractility in vitro: putative cGMP involvement.

1. Sildenafil citrate (Viagratrade mark; Pfizer, Sandwich, Kent, UK), a phosphodiesterase 5 inhibitor, rises cGMP levels in smooth muscle cells. It relaxes both vascular and visceral smooth muscle. In order to assess the intestinal effects of sildenafil, we decided to investigate its actions on rat duodenal motor activity in vitro. 2. In isolated duodenal segments maintained in Tyrode's solution, sildenafil exhibited a concentration-dependent antispasmodic effect on acetylcholine (ACh)-induced phasic contractions, with an IC50 value of 26.7 micromol/L (95% confidence interval (CI) 2.0-55.3 micromol/L). 3. Sildenafil also relaxed the carbamylcholine (CCh)-induced sustained contraction with an IC(50) of 16.2 micromol/L (95% CI 9.5-27.6 micromol/L). Sildenafil produced significant additional relaxation of 25.2 +/- 8.1% of the CCh-induced contraction, beyond basal tone. 4. Sildenafil reduced the amplitude of spontaneous duodenal contractions with an EC50 of 9.6 micromol/L (95% CI 5.7-16.2 micromol/L). This effect was significantly more potent than the effects of zaprinast and papaverine, which also reduced duodenal contractions with EC50 values of 91.6 micromol/L (95% CI 46.0-182.2 micromol/L) and 78.5 micromol/L (95% CI 37.1-166.3 micromol/L), respectively. 5. In preparations treated previously with methylene blue (10 micromol/L) or 1H-[1,2,4]oxadiazolo(4,3-a)quinoxalin-1-one (ODQ; 10 micromol/L), the EC50 values for the sildenafil effect were significantly increased to 39.0 micromol/L (95% CI 23.9-63.4 micromol/L) and 43.8 micromol/L (95% CI 24.5-78.3 micromol/L), respectively. These values were significantly greater than those obtained with sildenafil alone. 6. In conclusion, sildenafil has myorelaxant and antispasmodic effects on rat duodenal segments in vitro. The contractile inhibitory effect of sildenafil on rat isolated duodenum is probably due to intracellular cGMP accumulation as a result of its decreased degradation.