Armênio Aguiar dos Santos

By utilizing phenylephrine and prazosin in isolated rat aortas, students can better understand the concept of antagonist potency. This activity provides a practical opportunity to discuss key aspects of cell-drug interactions, including efficacy and intrinsic activity, via parameters such as EC ₅₀ , IC ₅₀ , equilibrium dissociation constant ( K _b ), and antagonist potency (pA ₂ ).

Volemic control is essential for maintaining tissue perfusion and fluid homeostasis, with cardiorenal and endothelial mediators regulating intravascular composition, often impaired in pathological states. Notably, intestinal epithelial cells are highly sensitive to volume fluctuations, resulting in changes in intestinal permeability that may not be detected by current diagnostic methods. This review offers a comprehensive description of the main mediators involved in volemic regulation, their impact on intestinal morphofunctionality, and specific details regarding epithelial cells. Additionally, key biomarkers - especially lactulose/mannitol - for assessing intestinal barrier disruption are highlighted, and a novel approach is proposed using liquid chromatography-mass spectrometry to investigate gut alterations in heart failure and exercise-induced stress, which are silent and neglected conditions with significant repercussions on intestinal barrier function.

Background The COVID-19 pandemic, caused by SARS-CoV-2, has unveiled a range of symptoms beyond the respiratory system, including significant gastrointestinal manifestations. Aims This study explores the prevalence and intensity of gastroesophageal symptoms in post-COVID-19 patients and the integrity of the esophageal epithelial barrier. Methods We conducted a prospective longitudinal cohort study with 55 patients hospitalized due to COVID-19 at a University Hospital. Patients were evaluated during hospitalization and between 3 and 6 months post-discharge, using validated questionnaires for gastrointestinal and gastroesophageal reflux symptoms. Additionally, 25 of these patients underwent upper digestive endoscopy, with esophageal mucosal biopsies analyzed for transepithelial electrical resistance (TER), permeability, and expression of inflammatory cytokines and cell junction proteins. Data expressed as mean EPM, inference by two-way ANOVA. Results Results were considered statistically significant at p < 0.05. There were significant increases in heartburn and acid reflux symptoms in post-COVID-19 patients, as measured by the GSRS questionnaire. Biopsies from post-COVID patients revealed increased esophageal permeability when compared to non-COVID patients in acidic media (pH 2: non-COVID-19: 717.8 ± 168.2 vs. post-COVID-19: 1377.6 ± 316.4), suggesting compromised mucosal barrier. Furthermore, IL-8 levels and expression of Claudin-2 were elevated in these patients. Conclusions The data suggested that COVID-19 infection may cause lasting damage to the esophageal epithelial barrier, increasing its permeability and provoking an exacerbated inflammatory response. These changes may explain the prevalence of post-infection gastroesophageal symptoms. Our findings underscored the importance of continuous monitoring and the development of therapeutic strategies to mitigate gastroesophageal effects in patients recovering from COVID-19. Graphical Abstract

Inflammatory bowel disease (IBD) induces immunological and autonomic imbalances. Exercise is a beneficial strategy for controlling IBD symptoms. We investigated the role of exercise on gastrointestinal (GI) motility changes and autonomic parameters in rats with ileitis. Rats were divided into control, ileitis, and exercise+ileitis groups. Ileitis was induced by TNBS (40 mM, intraileally). The exercise was swimming (1 h/day/4 weeks, 5%/bw). We assessed eating behaviour and oxidative stress. Body composition was assessed by bioimpedance. Autonomic balance and ECG parameters were measured by an electrocardiogram (ECG). Gastrointestinal motility was evaluated using the phenol red technique. In terms of body composition, total body water (TBW), body mass index (BMI), and fat-free mass (FFM) were higher in the ileitis group (216.80 ± 11.44 mL; 24.09 ± 2.15 g/cm²; 287.1 ± 14.66 g) (p < 0.05) vs. control rats (130.06 ± 28.23 mL; 16.38 ± 2.50 g/cm²; 193 ± 42.21 g) and exercise prevented (91.33 ± 12.33 mL; 11.73 ± 0.47 g/cm²; 133.8 ± 16.82 g) (p < 0.05) these changes. The exercise+ileitis group induces a reduction (p < 0.05) in gastric retention vs. ileitis and control (11.22 ± 1.91% vs. 35.17 ± 1.01% and 33.96 ± 1.77%). Ileitis increased intestinal retention in the duodenum (46.3 ± 2.56% vs. 24.98 ± 1.78%) and jejunum (34.22 ± 2.33% and 34.72 ± 2.83% vs. 47.32 ± 1.48%) (p < 0.05) and decreased intestinal retention in the ileum (p < 0.05) vs. the control group. Exercise+ileitis prevented (p < 0.05) changes in the duodenum (24.96 ± 1.66% vs. 46.3 ± 2.56%) and ileum (40.32 ± 3.75% vs. 14.08 ± 0.88%). Ileitis induces high MDA levels (p < 0.05) vs. control rats (4.43 ± 0.69 vs. 2.15 ± 0.12 nmol/mg of the tissue). This effect was prevented (p < 0.05) in the exercise+ileitis group (2.75 ± 0.21 vs. 4.43 ± 0.69 nmol/mg of the tissue). We observed a reduction in the LF component (p < 0.05) in the ileitis group vs. control group (31.32 ± 3.99 vs. 43.43 ± 3.86). The correlation indicated a stronger interrelationship between the autonomic parameter and intestinal retention in the ileum (r: 0.68; p: 0.04). The current study suggests intestinal ileitis alters GI motility and autonomic balance, and physical exercise can represent an essential non-pharmacological approach to IBD treatment.

Background/Objectives: Physical exercise can have significant consequences for the gastrointestinal tract, which is why there have been studies into its influence on the treatment of conditions such as colorectal cancer, inflammatory bowel diseases (IBD), and irritable bowel syndrome (IBS), being that there is epidemiological evidence that exercise has a protective effect against colon cancer. This review aims to demonstrate the mechanisms of action of physical exercise in the gastrointestinal tract, as well as the benefits of exercise in diseases associated with the digestive system, in addition to gathering training recommendations in treating different gastrointestinal diseases. Results: Physical exercise modulates gastrointestinal motility, permeability, immune responses, and microbiota composition, with both beneficial and adverse effects depending on intensity and duration. Regular moderate exercise is associated with improved quality of life in IBD and IBS, reduced colorectal cancer risk, and potential symptom relief in constipation. However, high-intensity exercise may exacerbate gastroesophageal reflux symptoms and increase the risk of gastrointestinal bleeding. While aerobic exercise has been extensively studied, the effects of resistance training on gastrointestinal health remain underexplored. Conclusions: New methodologies and techniques, such as molecular biology and the study of gastric receptors, have led to advances in understanding the gastrointestinal changes associated with physical exercise. These advances cover different exercise intensities and are being investigated in both experimental models and clinical studies.

We suggest a cardiogastric reflex with the participation of neuroendocrine mediators, which contributes to regulating liquid balance in the animal’s body. Atrial natriuretic peptide and oxytocin are substances recognized for participating in diuresis and regulating the transit of liquids in the gastrointestinal tract in situations of cardiac volume overload, as was simulated with atrial stretching in the present experimental model.

Dysfunction of the intestinal epithelium barrier (DIEB) is frequent and can lead to serious complications in early childhood when diagnosis and clinical intervention are limited, especially in children with environmental enteric disease and malnutrition. The use of refined analytical techniques is increasingly necessary in this context. This study aimed to validate the high-performance liquid chromatography method coupled with tandem mass spectrometry (LC-MS/MS) to measure DIEB by lactulose:mannitol ratio detection (LM test) in samples of children with different social profiles from Fortaleza, Ceará. The first experimental set was conducted to validate the method through laboratory parameters, such as limit of detection (LD), limit of quantification (LQ), specificity/selectivity, linearity, accuracy, and precision. All validation parameters achieved detection and recovery standards within an acceptable coefficient of variation. Community samples (human development index (HDI) from 0.000 to ≤0.499) were obtained from children from the cohort study Malnutrition-Enteric Diseases, Fortaleza-CE (environmental enteric disease; EED group). The control group samples came from a school located in a region with a high HDI (>0.8). Mannitol excretion was lower in the EED group than in the control group (P<0.0001). On the other hand, LM was higher in this group compared to the control group (P<0.0001). For the first time, a robust analytical approach was used to detect biomarkers of environmental enteropathy (LM) in community samples, confirming with high-sensitivity the damage to the intestinal epithelial barrier function in populations living in low socio-economic conditions.

The misuse of anabolic androgenic steroid associated or not with physical workouts disrupts gastrointestinal (GI) function homeostasis. Our goal was to investigate the effects of nandrolone decanoate (ND) and moderate swimming on the GI transit of solid meals, GI motor contractility, and intestinal histology in rats. Male Wistar rats were allocated to four groups that received intramuscular injections of ND (5.0 mg/kg) or vehicle (60.0 mu L) and were submitted or not to swimming sessions (60 min, 5% body weight overload) for 4 weeks. Gastric emptying, intestinal transit, in vitro GI contractility, intestinal morphometry, and duodenal mucosal mast cells were evaluated in all experimental groups. ND treatment accelerated gastric emptying, slowed small intestine transit time, enhanced gastric carbachol-mediated reactivity, decreased crypt depth and villus height, reduced mucosal thickness, and increased the circular and longitudinal muscle layer thickness of the duodenum in sedentary rats. Moderate exercise accelerated intestinal transit time and reduced submucosa thickness. In vehicle-treated animals, a strong negative correlation was found between intestinal transit and mucosal mast cells, which was reversed by ND treatment. Combining ND treatment and swimming accelerated gastric emptying, increased duodenal cholinergic reactivity, inhibited the sodium nitroprusside relaxing response, increased the number of duodenal mast cells, decreased villus height, and increased the thickness of all muscle layers. ND changed the morphological and functional properties of the GI tract over time, with intense dysmotility, especially in sedentary animals, but moderate exercise seemed to have played a compensatory role in these harmful effects in the gut.

Patients undergoing chemotherapy with cisplatin commonly present gastrointestinal effects such as constipation and gastric emptying (GE) delay. Both the purinergic system and physical exercise modulate the gastrointestinal (GI) tract. In the current study, we investigated the role of ATP, physical exercise, and P2X7 receptor blocking on GE delay induced by cisplatin in rats. Male rats were divided into the following groups: control (C), cisplatin (Cis), exercise (Ex), Brilliant Blue G (BBG), ATP, Cis+Ex, Cis+ATP, Cis+BBG, Cis+Ex+BBG, Cis+Ex+BBG+ATP, and Cis+ATP+BBG. GE delay was induced by treatment with 1 mg/kg cisplatin (1 time/week for 5 weeks, ip). The moderate physical exercise was swimming (1 h/day, 5 days/week for 5 weeks). At the end of the treatment or exercise and 30 min before the GE assessment, some groups received BBG (50 mg/kg, sc) or ATP (2 mg/kg, sc). Then, GE was assessed after a 10-min postprandial period. Chronic use of Cis decreased GE delay (P<0.05) compared to the control group. Both exercise and ATP prevented (P<0.05) GE delay compared to Cis. The pretreatment with BBG significantly inhibited (P<0.05) the effect of exercise and ATP. On the other hand, the association between exercise and ATP reversed (P<0.05) the effect of the BBG and prevented GE delay. Therefore, we suggest that both exercise and treatment with ATP activate P2X7 receptors and prevent GE delay induced by cisplatin in rats.

Diabetic-metabolic syndrome (MetS-D) has a high prevalence worldwide, in which an association with the rupture of the intestinal epithelium barrier function (IEBF) has been pointed out, but the functional and morphological properties are still not well understood. This study aimed to evaluate the impact of acute hyperglycemia diabetes on intestinal tight junction proteins, metabolic failure, intestinal ion and water transports, and IEBF parameters. Diabetes was induced in male Rattus norvegicus (200-310 g) with 0.5 mL of streptozotocin (70 mg/kg). Glycemic and clinical parameters were evaluated every 7 days, and intestinal parameters were evaluated on the 14th day. The MetS-D animals showed a clinical pattern of hyperglycemia, with increases in the area of villi and crypts, lactulose:mannitol ratio, myeloperoxidase (MPO) activity, and intestinal tissue concentrations of malondialdehyde (MDA), but showed a reduction in reduced glutathione (GSH) when these parameters were compared to the control. The MetS-D group had increased secretion of Na⁺, K⁺, Cl^-, and water compared to the control group in ileal tissue. Furthermore, we observed a reduction in mRNA transcript of claudin-2, claudin-15, and NHE3 and increases of SGLT-1 and ZO-1 in the MetS-D group. These results showed that MetS-D triggered intestinal tissue inflammation, oxidative stress, complex alterations in gene regulatory protein transcriptions of intestinal transporters and tight junctions, damaging the IEBF and causing hydroelectrolyte secretion.