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Disorders of gastrointestinal motility are the major physiologic problem in chagasic megacolon. The contraction mechanism is complex and controlled by different cell types such as enteric neurons, smooth muscle, telocytes, and an important pacemaker of the intestine, the interstitial cells of Cajal (ICCs). The role of ICCs in the progression of acute and chronic Chagas disease remains unclear. In the present work, we investigate the aspects of ICCs in a long-term model of Chagas disease that mimics the pathological aspects of human megacolon. Different subsets of ICCs isolated from Auerbach's myenteric plexuses and muscle layers of control and Trypanosoma cruzi infected animals were determined by analysis of CD117, CD44, and CD34 expression by flow cytometer. Compared with the respective controls, the results showed a reduced frequency of mature ICCs in the acute phase and three months after infection. These results demonstrate for the first time the phenotypic distribution of ICCs associated with functional dysfunction in a murine model of chagasic megacolon. This murine model proved valuable for studying the profile of ICCs as an integrative system in the gut and as a platform for understanding the mechanism of chagasic megacolon development.

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Constipation is a disorder of the gastrointestinal (GI) and some of the main etiological mechanisms are directly related to changes in GI physiology. The capacity to carry out paired assessments and measure GI parameters under the influence of constipation is a relevant point in selecting a suitable methodology. We aimed to perform a non-invasive investigation of gastrointestinal motility in constipated rats using the alternating current biosusceptometry system (ACB). The animals were split into two groups: the pre-induction stage (CONTROL) and post-induction loperamide stage (LOP). We assessed GI motility parameters using the ACB system. Colon morphometric and immunohistochemical analyses were performed for biomarkers (C-kit) for interstitial cells of Cajal (ICC). Our results showed a significant increase in gastrointestinal transit in the LOP group in addition to a reduction in the dominant frequency of gastric contraction and an arrhythmic profile. A change in colonic contractility profiles was observed, indicating colonic dysmotility in the LOP group. We found a reduction in the number of biomarkers for intestinal cells of Cajal (ICC) in the LOP group. The ACB system can evaluate transit irregularities and their degrees of severity, while also supporting research into novel, safer, and more efficient treatments for constipation.

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PURPOSE: To evaluate if the density of interstitial cells of Cajal (ICC) in the ureteropelvic junction (UPJ) influences the outcomes of pyeloplasty in adults. METHODS: Twenty-three patients with the diagnosis of ureteropelvic junction obstruction (UPJO) that underwent laparoscopic dismembered pyeloplasty were included. ICC density was measured using immunohistochemistry reaction for c-KIT expression in the resected UPJ segment. Pyeloplasty outcome was evaluated by patient self-report pain, urinary outflow using DTPA renogram and hydronephrosis assessment using ultrasound (US) at 12 months of follow-up. A logistic regression analysis was performed to assess the association of pyeloplasty outcomes and ICC density. RESULTS: Low, moderate, and high ICC density were present in 17.4%, 30.4%, and 52.2% of the patients, respectively. Complete pain resolution was observed in 100%, 85.7%, and 75% of patients with low, moderate and high ICC density, respectively (p = 0.791). DTPA renogram improved in 75%, 85.7%, and 91.7% of patients with low, moderate and high ICC density, respectively (p = 0.739). Hydronephrosis improved in 25%, 85.7%, and 91.7% of patients with low, moderate and high ICC density, respectively (p = 0.032). CONCLUSIONS: Patients with high ICC density have a significant amelioration of hydronephrosis after pyeloplasty. However, ICC density is not associated with functional outcomes.

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Introducción: Los tumores del estroma gastrointestinal son neoplasias de comportamiento benigno o maligno. Se originan de las células intersticiales de Cajal del tubo digestivo. Objetivo: Describir dos formas distintas de presentación clínica de los tumores del estroma gastrointestinal. Casos clínicos: El caso 1, paciente femenina de 65 años de edad que acudió por síntomas compresivos del tubo digestivo superior a causa de un gastrointestinal gástrico. El caso 2, paciente masculino de 56 años de edad que acudió por sangrado de tubo digestivo medio ocasionado por un gastrointestinal intestinal. Conclusiones: Los tumores del estroma gastrointestinal tienen distinta presentación clínica. Su tratamiento es esencialmente quirúrgico y en algunos casos complementados con terapia molecular dirigida(AU)

Introduction: Gastrointestinal stromal tumors are neoplasms of benign or malignant behavior. They originate from the interstitial cells of Cajal in the digestive tract. Objective: The objective of this work is to describe two different forms of clinical presentation. Case report: case 1: 65-year-old female patient who presented for compression symptoms of the upper digestive tract due to gastric GIST; case 2: 56-year-old male who presented with bleeding from the middle digestive tract caused by intestinal GIST. Conclusions: GISTs have different clinical presentation. Its treatment is essentially surgical and in some cases supplemented with targeted molecular therapy(AU)

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Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disease caused by a mutation in the IDUA gene, which codes α-L-iduronidase (IDUA), a lysosomal hydrolase that degrades two glycosaminoglycans (GAGs): heparan sulfate (HS) and dermatan sulfate (DS). GAGs are macromolecules found mainly in the extracellular matrix and have important signaling and structural roles which are essential to the maintenance of cell and tissue physiology. Nondegraded GAGs accumulate in various cell types, which characterizes MPS I as a multisystemic progressive disease. Many tissues and vital organs have been described in MPS I models, but there is a lack of studies focused on their effects on the reproductive tract. Our previous studies indicated lower sperm production and morphological damage in the epididymis and accessory glands in male MPS I mice, despite their ability to copulate and to impregnate females. Our aim was to improve the testicular characterization of the MPS I model, with a specific focus on ultrastructural observation of the different cell types that compose the seminiferous tubules and interstitium. We investigated the testicular morphology of 6-month-old male C57BL/6 wild-type (Idua+/+) and MPS I (Idua-/-) mice. We found vacuolated cells widely present in the interstitium and important signs of damage in myoid, Sertoli and Leydig cells. In the cytoplasmic region of Sertoli cells, we found an increased number of vesicles with substrates under digestion and a decreased number of electron-dense vesicles similar to lysosomes, suggesting an impaired flux of substrate degradation. Conclusions: Idua exerts an important role in the morphological maintenance of the seminiferous tubules and the testicular interstitium, which may influence the quality of spermatogenesis, having a greater effect with the progression of the disease.

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Los tumores del estroma gastrointestinal (TEGI) son las neoplasias mesenquimales más frecuentes del tracto digestivo con una frecuencia de 0,1 a 3 % de todas las neoplasias gastrointestinales. Son derivadas de las células intersticiales de Cajal, localizadas a lo largo del plexo mioentérico de la pared intestinal. Comprenden leiomisarcomas, leiomioblastomas, leimiomas, schwannomas. Están formadas por células fusiformes, en la mayoría, epitelioides o ambas. Se localizan predominantemente en estómago e intestino delgado. Inmunohistoquimicamente se detecta expresión de receptores KIT (antígeno CD117) que puede ser focal, variable o difusa. Involucran tumores benignos pero con potencial malignidad hasta sarcomas metastizantes. Su pronóstico se basa el tamaño y porcentaje de mitosis. La sintomatología depende del lugar de origen, en este caso como masa palpable abdominal y obstrucción intestinal. El tratamiento es la resección completa con márgenes limpios. En caso de metástasis preoperatoria, esta no cambia la conducta quirúrgica, debido a la posibilidad de obstrucción y sangrado. El Imatinib a dosis de 400 mg controla el crecimiento eventual de enfermedad residual. Se presenta el caso clínico de paciente con masa abdominal y cuadro de obstrucción intestinal que evoluciona a la perforación de un TEGI localizado en yeyuno proximal con cuadro peritoneal y absceso subfrenico. Se procede a resección intestinal con yeyuno yeyuno anastomosis resección completa. La histopatología reporta Tumor estronal gastrointestinal y la inmunohistoquimica Neoplasia Fusocelular. CONCLUSION: Los TEGI son de origen mesenquimal, comprenden espectro grande de tumores desde benignos, hasta carcomas altamente malignos. Los factores pronósticos se asocian al tamaño e índice mitótico del tumor. La inmunohistoquimica reporta su expresión para CD117. La resección quirúrgica completa es el pilar de tratamiento y en casos de resección incompleta o irresecabilidad puede usarse imatinib.

Gastrointestinal stromal tumors (GIST) are the most frequent mesenchymal neoplasms of the digestive tract with a frequency of 0.1 to 3% of all gastrointestinal neoplasms. They are derived from the interstitial cells of Cajal, located along the myoenteric plexus of the intestinal wall. They include leiomysarcomas, leiomioblastomas, leimiomas, schwannomas. They are made up of spindle cells, in the majority, epithelioids or both. They are located predominantly in the stomach and small intestine. Immunohistochemically, KIT receptor expression (CD117 antigen) is detected, and they can be focal, variable or diffuse. They involve benign but potentially malignancy tumors up to metastatic sarcomas. Their prognosis is based on the size and percentage of mitosis. The symptoms depend on the place of its origin. Treatment is complete resection with clean margins. In the case of preoperative metastases, this does not change the surgical approach, due to the possibility of obstruction and bleeding. Imatinib at a dose of 400 mg controls the eventual growth of residual disease. We present the clinical case of a patient with an abdominal mass and a small bowel obstruction that progresses to perforation of a GIST located in the proximal jejunum with a peritonitis and subphrenic abscess. Intestinal resection is performed with jejunum jejunoanastomosis and complete resection. Histopathology reports gastrointestinal stromal tumor and immunohistochemistry, Fusocellular neoplasia. Conclusion: GIST are of mesenchymal origin, they include a wide spectrum of tumors from benign to highly malignant sarcomas. Prognostic factors are associated with tumor size and mitotic index. Immunohistochemistry reports its expression for CD117. Complete surgical resection is the mainstay of treatment and in cases of incomplete resection or unresectability imatinib can be used.

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BACKGROUND: Serotonin (5-HT) is present in the epithelial enterochromaffin cells (EC), mast cells of the lamina propria and enteric neurons. The 5-HT is involved in regulating motility, secretion, gut sensation, immune system and inflammation. OBJECTIVE: Evaluate the effects of diabetes and quercetin supplementation on serotoninergic cells and its cell loss by apoptosis in jejunal mucosa of streptozotocin-induced diabetic rats (STZ-rats). METHODS: Twenty-four male Wistar rats were divided into four groups: normoglycemic (C), normoglycemic supplemented with 40 mg/day quercetin (Q), diabetic (D) and diabetic supplemented with 40 mg/day quercetin (DQ). After 120 days, the jejunum was collected and fixated in Zamboni's solution for 18 h. After obtaining cryosections, immunohistochemistry was performed to label 5-HT and caspase-3. Quantification of 5-HT and caspase-3 immunoreactive (IR) cells in the lamina propria, villi and crypts were performed. RESULTS: The diabetic condition displayed an increase of the number of 5-HT-IR cells in villi and crypts, while decreased number of these cells was observed in lamina propria in the jejunum of STZ-rats. In the diabetic animals, an increased density of apoptotic cells in epithelial villi and crypts of the jejunum was observed, whereas a decreased number of caspase-3-IR cells was observed in lamina propria. Possibly, quercetin supplementation slightly suppressed the apoptosis phenomena in the epithelial villi and crypts of the STZ-rats, however the opposite effect was observed on the 5-HT-IR cells of the lamina propria. Quercetin supplementation on healthy animals promoted few changes of serotoninergic function and apoptotic stimuli. CONCLUSION: These results suggest that quercetin supplementation mostly improved the serotonergic function affected by diabetes maybe due to antioxidant and anti-inflammatory properties of quercetin.

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The objective was to study the effect of mechanical intestinal obstruction in rats on the phenotype of interstitial cells of Cajal (ICC). Healthy Wistar rats were randomly divided into sham-operation group (C), one day obstruction group (M1), two days obstruction group (M2), and three days obstruction group (M3), with 10 rats in each group. The expression of SCF mRNA and c-Kit protein in intestinal tissue was investigated by RT-PCR and immunohistochemistry. Compared with the sham-operation group, the relative expression of SCF mRNA and the expression of c-Kit protein in intestinal tissue were significantly decreased in both obstruction groups. Levels decreased gradually with the prolongation of obstruction time, and significantly decreased on the 3rd day after obstruction (P<0.05). Immunohistochemical staining of the small intestine showed that the number of ICC in the sham-operation group was the highest, and they were gradually decreased with the extension of obstruction time in the M1 to M3 groups. There was a significant difference between groups (P<0.05). Intestinal obstruction caused a decrease in the concentrations of SCF mRNA and c-Kit protein in ICC. With the prolongation of intestinal obstruction, the number of ICCs gradually decreased.

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ABSTRACT BACKGROUND: Serotonin (5-HT) is present in the epithelial enterochromaffin cells (EC), mast cells of the lamina propria and enteric neurons. The 5-HT is involved in regulating motility, secretion, gut sensation, immune system and inflammation. OBJECTIVE: Evaluate the effects of diabetes and quercetin supplementation on serotoninergic cells and its cell loss by apoptosis in jejunal mucosa of streptozotocin-induced diabetic rats (STZ-rats). METHODS: Twenty-four male Wistar rats were divided into four groups: normoglycemic (C), normoglycemic supplemented with 40 mg/day quercetin (Q), diabetic (D) and diabetic supplemented with 40 mg/day quercetin (DQ). After 120 days, the jejunum was collected and fixated in Zamboni's solution for 18 h. After obtaining cryosections, immunohistochemistry was performed to label 5-HT and caspase-3. Quantification of 5-HT and caspase-3 immunoreactive (IR) cells in the lamina propria, villi and crypts were performed. RESULTS: The diabetic condition displayed an increase of the number of 5-HT-IR cells in villi and crypts, while decreased number of these cells was observed in lamina propria in the jejunum of STZ-rats. In the diabetic animals, an increased density of apoptotic cells in epithelial villi and crypts of the jejunum was observed, whereas a decreased number of caspase-3-IR cells was observed in lamina propria. Possibly, quercetin supplementation slightly suppressed the apoptosis phenomena in the epithelial villi and crypts of the STZ-rats, however the opposite effect was observed on the 5-HT-IR cells of the lamina propria. Quercetin supplementation on healthy animals promoted few changes of serotoninergic function and apoptotic stimuli. CONCLUSION: These results suggest that quercetin supplementation mostly improved the serotonergic function affected by diabetes maybe due to antioxidant and anti-inflammatory properties of quercetin.

RESUMO CONTEXTO: A serotonina (5-HT) está presente nas células epiteliais enterocromafins (CE), nos mastócitos da lâmina própria e nos neurônios entéricos. A 5-HT está envolvida na regulação da motilidade, secreção, nocepção intestinal, sistema imunológico e inflamação. Objetivo: Avaliar os efeitos do diabetes e da suplementação de quercetina sobre a função serotoninérgica e a perda celular por apoptose na mucosa jejunal de ratos diabéticos induzidos por estreptozotocina (ratos STZ). MÉTODOS: Vinte e quatro ratos Wistar machos foram divididos em quatro grupos: normoglicêmico (C), normoglicêmico suplementado com quercetina 40 mg/dia (Q), diabético (D) e diabético suplementado com quercetina 40 mg/dia (DQ). Após 120 dias, o jejuno foi coletado e fixado na solução de Zamboni por 18 horas. Após a obtenção de cortes em criostato, a imuno-histoquímica foi realizada para marcar 5-HT e caspase-3. A quantificação de células imunorreativas (IR) à 5-HT e caspase-3 foram realizadas na lâmina própria, vilosidades e criptas. RESULTADOS: A condição diabética ocasionou um aumento do número de células 5-HT-IR nas vilosidades e criptas, enquanto que na lâmina própria houve uma redução dessas células, no jejuno de ratos STZ. Nos animais diabéticos, foi observada uma densidade aumentada de células apoptóticas no epitélio do jejuno, tanto nas vilosidades quanto nas criptas, por outro lado um número reduzido de células caspase-3-IR foi observado na lâmina própria. Possivelmente, a suplementação de quercetina suprimiu ligeiramente os fenômenos de apoptose no epitélio de vilosidades e criptas do jejuno de ratos STZ, no entanto, o efeito oposto foi observado nas células 5-HT-IR da lâmina própria. A suplementação com quercetina em animais saudáveis promoveu poucas alterações na função serotoninérgica e nos estímulos apoptóticos. CONCLUSÃO: Estes resultados sugerem que a suplementação de quercetina melhorou principalmente a função serotoninérgica afetada pelo diabetes, talvez devido às propriedades antioxidantes e anti-inflamatórias da quercetina.

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