Refractory iron deficiency anemia as an early manifestation of autoimmune gastritis in a teenager / Anemia ferropénica refractaria como presentación temprana de gastritis autoinmune en un adolescente

Abstract Autoimmune gastritis is an underdiagnosed disease in the pediatric population due to the absence of specific signs and symptoms and late clinical manifestations. Iron deficiency anemia has recently been identified as an early hematological manifestation, allowing an early diagnostic approach. We present the case of a Colombian teenager, with no history of autoimmunity, with refractory iron deficiency. He underwent extension studies; biopsies and serology compatible with autoimmune gastritis were documented, requiring parenteral iron in its evolution. This pathology is underdiagnosed in our context since early diagnosis requires a high index of suspicion to prevent associated complications.

Resumen La gastritis autoinmune es una enfermedad subdiagnosticada en la población pediátrica. Lo anterior se debe a la ausencia de signos y síntomas específicos y manifestaciones clínicas tardías. Recientemente se ha identificado la anemia ferropénica como una manifestación hematológica precoz, lo que permite un enfoque diagnóstico temprano. Se presenta el caso de un adolescente colombiano, sin antecedentes de autoinmunidad, con ferropenia refractaria, en el que se realizaron estudios de extensión y se documentaron biopsias y serología compatible con gastritis autoinmune, con requerimiento de hierro parenteral en su evolución. Esta patología es subdiagnosticada en nuestro medio, ya que el diagnóstico temprano requiere un alto índice de sospecha, lo que permite la prevención de las complicaciones asociadas.

Mechanism of Bmal1 Involved in Irritable Bowel Syndrome via TPH1-5-HT Signaling Pathway in Enterochromaffin Cells / 胃肠病学

Background: Disrupted circadian rhythms have been associated with the development of irritable bowel syndrome (IBS). In some IBS patients, the symptoms may present with circadian fluctuations. Enterochromaffin cells (EC cells) and tryptophan hydroxylase 1 (TPH1) - 5 - hydroxytryptamine (5 - HT) signaling pathway are currently recognized as the key pathophysiological mechanism of IBS. Aims: To explore whether Bmal1, the core circadian clock gene, is involved in the occurrence of IBS by regulating TPH1-5-HT signaling pathway in EC cells. Methods: Normal Sprague-Dawley (SD) rats and IBS-model SD rats, as well as wild type (WT) and intestine-specific Bmal1 knockout (Bmal1

Role and Mechanism of Colon Circadian Clock Gene Bmal1 Involved in Symptoms of Irritable Bowel Syndrome With Diarrhea / 胃肠病学

Background: Symptoms of irritable bowel syndrome with diarrhea (IBS-D) are known to be influenced by circadian oscillation; however, the pathophysiological mechanism is still unclear. Aims: To investigate the role and underlying mechanism of colon circadian clock gene Bmal1 involved in the occurrence of symptoms in IBS-D patients. Methods: Forty-six patients with IBS-D and 34 normal controls from Army Medical Center of PLA during September 2018 to February 2021 were recruited in this study. IBS-severity scoring system (IBS-SSS) was used to evaluate the severity of IBS-D symptoms. A colonoscopy was performed to obtain biopsy specimens from rectosigmoid colon. The concentration of 5-hydroxytryptamine (5-HT), and expressions of Bmal1 and chromogranin A (CgA), a biomarker of enterochromaffin cells (EC cells), in colonic mucosa were detected by ELISA and double-labeled immunofluorescence, respectively. Results: Both the 5-HT concentration and number of EC cells in colonic mucosa of IBS-D patients were significantly higher than those of the normal controls (all P< 0.05). Bmal1 was mainly expressed in intestinal epithelial cells and was highly expressed in EC cells. Co-expression of Bmal1 and CgA was observed. Compared with the normal control group biopsied at the same time point, expression of Bmal1 was significantly higher in specimens taken at 9 a.m., and expression of Bmal1 was significantly lower in specimens taken at 17 p.m. in IBS-D patients (all P< 0.05). Spearman correlation coefficient analysis showed that Bmal1 expression at 9 a.m. was positively correlated with the total score of IBS-SSS and subscore of abdominal pain and discomfort (r

Distribution of serotonin-immunoreactive enterochromaffin cells in the gastrointestinal tract of the least shrew (Cryptotis parva) / Distribución de las células enterocromafines serotonina-inmunorreactiva del tracto gastrointestinal de la musaraña enana (Cryptotis parva)

Serotonin is an important neurotransmitter in the central (CNS) and peripheral (PNS) nervous systems. It is involved in a variety of physiological processes both in the gut and in the CNS. The present study examined the distribution of serotonin containing enterochromaffin cells in the gastrointestinal tract (GIT) of a vomit competent species, the least shrew. These cells were easily recognized by their globular granules stained with the H&E and serotonin immune-positive stain. The immunoreactive enterochromaffin cells (IERCs) were mainly confined to the basal portion of the glandular epithelium and were distributed throughout the shrew stomach, small and large intestine. None was found to be associated with the mucosal epithelial lining. Moreover, their distribution and count varied in different regions of the GIT suggesting specific functions for these regions. The highest concentration of IERCs was found in the colon followed by the Jejunum. Appreciable numbers of IERCs were found in the stomach especially at the esophageo-gastric junction. The gastric location of the IERCs was mainly in the basal portion of the gland. However, some IERCs were associated with the parietal cells of the stomach. Two types of IERCs were observed: One with globular secretory granules in their apical portion of the cytoplasm which were located within the glandular epithelial cells facing the glandular lumen which release their secretions into the lumen; and the second were basally located, facing the lamina propria of the mucosa. Their secretory granules were not distinct in shape, and are most probably paracrine in their mode of secretions...

La serotonina es un importante neurotransmisor del sistema nervioso central (SNC) y periférico (SNP). Está implicado en una variedad de procesos fisiológicos, tanto en el intestino y el SNC. El presente estudio examinó la distribución de la serotonina contenida en las células enterocromafines del tracto gastrointestinal (TGI) de una especie competente al vómito, la musaraña enana. Estas células se reconocen fácilmente por sus gránulos globulares teñidas con H-E y la inmuno-tinción positiva para serotonina. Las células enterocromafines inmunorreactivas (CEI) se limitan principalmente a la parte basal del epitelio glandular y se distribuyeron por todo el estómago, intestino delgado e intestino grueso de la musaraña. Ninguna célula se encontró asociada al revestimiento epitelial mucoso. Además, su distribución y el recuento varió en diferentes regiones del TGI sugiriendo funciones específicas de estas regiones. La mayor concentración de CEI se encuentran en el colon seguido por el yeyuno. Números apreciables de CEI se encontraron en el estómago, especialmente en la unión esofago-gástrica. La ubicación de las CEI gástricas fue principalmente en la porción basal de la glándula. Sin embargo, algunas CEI se asociaron con las células parietales del estómago. Dos tipos de CEI se observaron, una con gránulos secretores globulares en su porción apical del citoplasma que se encuentra dentro de las células epiteliales glandulares que enfrenta el lumen glandular que liberan sus secreciones en el lumen, y el segundo se encuentra basalmente, frente a la lámina propia de la mucosa. Sus gránulos secretores no fueron diferentes en forma, y probablemente son más paracrinas en su modo de secreción...

Stress-induced Alterations in Mast Cell Numbers and Proteinase-activated Receptor-2 Expression of the Colon: Role of Corticotrophin-releasing Factor

This study was performed in order to assess whether acute stress can increase mast cell and enterochromaffin (EC) cell numbers, and proteinase-activated receptor-2 (PAR2) expression in the rat colon. In addition, we aimed to investigate the involvement of corticotrophin-releasing factor in these stress-related alterations. Eighteen adult rats were divided into 3 experimental groups: 1) a saline-pretreated non-stressed group, 2) a saline-pretreated stressed group, and 3) an astressin-pretreated stressed group. The numbers of mast cells, EC cells, and PAR2-positive cells were counted in 6 high power fields. In proximal colonic segments, mast cell numbers of stressed rats tended to be higher than those of non-stressed rats, and their PAR2-positive cell numbers were significantly higher than those of non-stressed rats. In distal colonic segments, mast cell numbers and PAR2-positive cell numbers of stressed rats were significantly higher than those of non-stressed rats. Mast cell and PAR2-positive cell numbers of astressin-pretreated stressed rats were significantly lower than those of saline-pretreated stressed rats. EC cell numbers did not differ among the three experimental groups. Acute stress in rats increases mast cell numbers and mucosal PAR2 expression in the colon. These stress-related alterations seem to be mediated by release of corticotrophin-releasing factor.

Significance of physiologic changes of quantity of enterochromaffin cells and expression of 5-hydroxytryptamine receptor 3 (5-HT3R) in SD rats at different ages / 中华老年医学杂志

Objective To study the changes of intestinal transit rate, quantity of enterochromaffin cells and expressions of 5-hydroxytryptamine receptor 3 (5-HT3R) in SD rats at different ages, and to investigate the possible mechanism of gastrointestinal dysfunction in aged rats. Methods Eighty healthy SD rats were divided into five groups: three months age, nine months age, eighteen months age, twenty-four months age and thirty months age,and there were sixteen rats in each group. The intestinal transit rate was detected. Immunohistochemistry staining was used to test the quality of chromaffin cells in mucosa and submucosa of jejunum, ileum and colon and to detect the expressions of 5-HT3R in intestinal myenteric plexus. Results The intestinal transit rate was significantly lower in thirty months age group than in three months age group [(52.1±9.8)% vs. (67.2±13.5)%, t=7.013, P=0.001]. In thirty months age group, the quality of chromaffin cells in mucosa and submueosa of jejunum, ileum and colon were 11.1±3.0, 10.6±1.9, 10.2±4.3, respectively, which were reduced compared with three months age group (22.9±6.2, 25.8±7.1, 23.0±5.7, t=3. 640,3. 384,4. 154, all P<0.01). The expressions of 5-HT3R in myenteric plexus of jejunum and ileum were reduced in thirty months age group than in nine months age group [4.8±1.4, 9.3±4.2 vs. 8.9±1.5, 14.5±5.3;t=3.464, 3.003,all P<0.01]. The expression of 5-HT3R in colon myenteric plexus were 5.0±1.3 and 9.0±1.7 in thirty months age group and three months age group, respectively (t=4.549,P<0.001). Conclusions In aged rats, the intestinal transit rate, quantity of enterochromaffin cells and expressions of 5-HT3R are decreased with ageing, and the gastrointestinal dysfunction may be associated with the changing of the quantity of enterochromaffin cells and expressions of 5-HT3R in myenteric plexus.