Colitis eosinofílica asociada a enfermedad inflamatoria intestinal / Eosinophilic colitis associated with inflammatory bowel disease

INTRODUCCIÓN: La colitis eosinofílica y la colitis de la enfermedad inflamatoria intestinal, son dos entidades que pueden compartir similares características clínicas, endoscópicas y terapéuticas pero diferentes criterios diagnósticos. OBJETIVOS: Describir el caso clínico de un niño preescolar con antecedente de alergia alimentaria, de hospitalizaciones y uso de antibióticos por varias ocasiones, que evoluciona con diarrea crónica intermitente. CASO CLÍNICO: Se trata de un paciente masculino, de 3 años 5 meses, con antecedente de alergia alimentaria con cuadro crónico de dolor abdominal, diarrea y retraso en el crecimiento. Se realiza abordaje de diarrea crónica. RESULTADOS: Con hallazgos clínicos de enfermedad inflamatoria intestinal y descripción histopatológica de colitis eosinofílica, se considera la asociación entre estas dos patologías sin dejar la posibilidad de que esta última se trate de una fase inicial de enfermedad inflamatoria intestinal. CONCLUSIONES: El tratamiento de pacientes con colitis eosinofílica complicada es similar a la enfermedad inflamatoria intestinal, se requiere seguimiento clínico, endoscópico e histopatológico de pacientes con colitis eosinofílica a largo plazo.

INTRODUCTION: Eosinophilic colitis and inflammatory bowel disease colitis are two entities that may share similar clinical, endoscopic and therapeutic features but different diagnostic criteria. OBJECTIVES: To describe the clinical case of a preschool child with a history of food allergy, hospitalizations and use of antibiotics for several occasions, who evolves with chronic intermittent diarrhea. CLINICAL CASE: This is a male patient, 3 years 5 months old, with a history of food allergy with chronic abdominal pain, diarrhea and growth retardation. Chronic diarrhea was approached. RESULTS: With clinical findings of inflammatory bowel disease and histopathological description of eosinophilic colitis, the association between these two pathologies is considered without leaving the possibility that the latter is an initial phase of inflammatory bowel disease. CONCLUSIONS: The treatment of patients with complicated eosinophilic colitis is similar to inflammatory bowel disease, clinical, endoscopic and histopathological follow-up of patients with eosinophilic colitis is required in the long term.

Relationship between chronic constipation and brain-gut microflora axis / 中华胃肠外科杂志

The role of the brain-gut microbiota axis in functional gastrointestinal diseases has been gradually recognized. According to the ROME IV diagnostic criteria, functional gastrointestinal diseases are classified as diseases caused by abnormal brain-gut interaction. This concept is of great significance to the change of diagnosis and treatment paradigm of functional gastrointestinal diseases. Chronic constipation is the most common functional gastrointestinal disease. The pathogenesis of chronic constipation is closely related to the imbalance of intestinal flora, the abnormality of enteric nervous system and neurotransmitter in brain. Therefore, in the diagnosis and treatment of chronic constipation, enough attention should be paid to the concept of integration of brain-gut microflora axis, but the clinical application of brain-gut microflora axis is still limited. This may be one of the factors for high incidence but poor treatment efficacy of chronic constipation. Based on the global research progress and our clinical experience, this article expounds the clinical significance of the brain-gut microbiota axis in chronic constipation.

Quantification of the neurons of myenteric plexus of the bat molossus rufus / Quantificação dos neurônios do plexo mientérico de morcegos da espécie Molossus rufus

There are no studies that characterize the enteric nervous system (ENS) bats. The organization and density of myenteric neurons may vary according to the animal species, as well as the segment of the digestive tube considered. The nitric oxide is one of the key neurotransmitters present in the myenteric neurons, acting as a mediator in the smooth muscle relaxation. These neurons are evidenced by immunohistochemistry of nitric oxide synthase (NOS) or by NADPH-diaphorase histochemistry. In this sense, this study aimed to characterize the total neuronal population and subpopulation NADPH-d+ of the myenteric plexus present in the jejunum of the insectivore species Molossus rufus quantitatively. Five specimens were collected of M. rufus in a buffer area of the "Reserva Biológica das Perobas" in the microregion of Cianorte/PR. After the euthanasia, in a chamber saturated with isoflurane, segments were collected from the small intestine corresponding to the jejunum intended for two techniques for neuronal marking, Giemsa and NADPH-diaphorase, and a fragment to the histological technique of hematoxylin-eosin and Masson's trichrome. All the procedures were approved by the "Comitê de Ética no Uso de Animais Unipar" (CEUA - protocol No. 34347/2017) and the "Instituto Chico Mendes de Conservação da Biodiversidade" (ICMBio - protocol No. 60061-1) The histological sections allowed to highlight the location of the myenteric plexus between the longitudinal and circular layers of the muscular tunic. The myenteric plexus had an average of total neuronal population (neurons Giemsa+) of 279.23 neurons/mm2, being the nitrergic neurons (neurons NADPH-d+) represented 20.4% of this total population, with an average of 58.14 neuron/mm2. Therefore, the collected data are consistent with previous studies in other mammalian species concerning the location of the myenteric plexus, as well as the neural myenteric proportion NADPH-d+ compared with the population of neurons Giemsa+. The gaps in the knowledge of ENS of bats limits comparative intraspecific and interspecific studies.(AU)

Não há estudos que caracterizem o sistema nervoso entérico (SNE) destes animais, configurando uma lacuna no conhecimento quanto à biologia destes indivíduos. A organização e densidade dos neurônios mientéricos podem variar de acordo com a espécie animal bem como o segmento do tubo digestório considerado. O óxido nítrico é um dos principais neurotransmissores presentes nos neurônios mientéricos, atuando como mediador no relaxamento do músculo liso gastrointestinal, de modo que estes neurônios são evidenciados igualmente pela imunohistoquímica da óxido nítrico-sintase (NOS) ou pela histoquímica da NADPH-diaforase. Neste sentido, objetivou-se caracterizar quantitativamente a população neuronal total e subpopulação NADPH-d+ do plexo mientérico presente no jejuno da espécie Molossus rufus de hábito alimentar insetívoro. Foram coletados cinco espécimes de M. rufus em área de amortecimento da Reserva Biológica das Perobas na microrregião de Cianorte/PR. Após a eutanásia, em câmara saturada com isoflurano, foram coletados segmentos do intestino delgado correspondentes ao jejuno destinados a duas técnicas para marcação neuronal, Giemsa e NADPH-diaforase e, um fragmento para a técnica histológica de hematoxilina-eosina e tricômio de Masson. Todos os procedimentos realizados foram aprovados pelo Comitê de Ética no Uso de Animais da Unipar (CEUA - protocolo nº 34347/2017) e pelo Instituto Chico Mendes de Conservação da Biodiversidade (ICMBio - protocolo nº 60061-1) Os cortes histológicos possibilitaram evidenciar a localização do plexo mientérico entre os estratos longitudinal e circular da túnica muscular. Neurônios Giemsa+ apresentaram uma média de 279,23 neurônios/mm2, já os neurônios nitrérgicos apresentaram em média 20,4% da população neuronal mientérica total, sendo evidenciados 58,14 neurônios NADPH-d+/mm2. Portanto, os dados coletados mostram-se condizentes com estudos anteriores em outras espécies de mamíferos quanto à localização do plexo mientérico, bem como, a proporção neuronal mientérica NADPH-d+ comparada com a população de neurônios Giemsa+. As lacunas existentes quanto ao conhecimento do SNE de morcegos limita possíveis inferências em comparativo intraespecífico e interespecífico.(AU)

Enfermedad de Hirschsprung y apendicitis en paciente pediátrico: reporte de caso / Hirschprungs diseases and appendicitis in pediatric patient: case report

La enfermedad de Hirschsprung es una malformación del sistema nervioso entérico, caracterizada por falta de células ganglionares en plexo submucoso y mientérico en pared distal del colon. En el 80% solo existe afectación del recto-sigma, sin embargo, pueden encontrarse casos de aganglionosis total. Reporte de Caso: Se presenta pre-escolar masculino de 4 años de edad, procedente de La Iguala, Lempira, Honduras, con historia de constipación y distensión abdominal de dos años de evolución, que ha empeorado progresivamente, y se atenuaba con el uso de enemas cada dos días para poder defecar. En mayo de 2016 llega al Hospital Mario Catarino Rivas, donde se le realizó una laparotomía exploratoria de emergencia debido a la presencia de deterioro clínico por constipación y distensión abdominal, acompañada de vómitos con restos alimenticios y fiebre alta de una semana de evolución. En dicha operación se realizó colectomía parcial izquierda, además se realizó una colostomía terapéutica y se diagnósticó enfermedad de Hirs-chsprung mediante biopsia, además del hallazgo incidental de apendicitis, se realizó apendicectomía obteniendo en general, una evolución satisfactoria.El estudio histopatológico de la biopsia del recto es el estándar de oro para realizar el diagnóstico. La ausencia de células ganglionares en el plexo submucoso con latinción hematoxilina y eosina establece el diagnóstico. El tratamiento de la enfermedad de Hirschsprung es de tipo quirúrgico y se busca la eliminación del segmento colónico afectado, de manera que se pueda lograr una anastomosis del colon proximal y distal al área agangliónica...(AU)

Effects and pathophysiological significance of intestinal flora on the enteric neuro-endocrine-immune system / 生理学报

Interactions among the nervous, the endocrine and the immune systems enable the gut to respond to the dietary products, pathogens and microbiota, which maintains the homeostasis of the body. However, dysbiosis may induce or aggravate the gastrointestinal (GI) and extra-GI diseases through changing the activities of enteric nervous system (ENS), enteroendocrine cells and enteric immune cells. Here we review recent advances in the understandings on how intestinal flora may impact the enteric neuro-endocrine-immune system in the gut, thereby contributing to the regulation of pathophysiological processes.

Unique characteristics of "the second brain" - The enteric nervous system / 生理学报

Enteric nervous system (ENS) is composed of intestinal submucosal and myenteric plexuses. ENS may independently regulate intestinal digestive and absorptive function, and it is also known as "the second brain" or gut brain. ENS has significant specificity relative to central nervous system (CNS) in properties and functional activities of neurons and neural circuits. ENS is connected with CNS through the feedback pathway (brain-gut-axis) of sympathetic and parasympathetic nerves and peripheral primary sensory afferent nerves to form the bidirectional brain-gut-axis, which may affect emotion, appetite and behavioral states of individuals. Gastrointestinal functional disorder (GIFD) induced by ENS dysfunction may not only cause abnormal gastrointestinal function but also has been implicated in cognitive and mood disorders, such as irritable bowel syndrome (IBS). GIFD would influence deeply the quality of life in patients. Nevertheless, in the worldwide, ENS has so far received much less attention as compared with CNS. The depth of research and scale of investment in ENS studies have been much lower than those in CNS studies. The situation in China is even more evident. From ENS research history, an outstanding problem is to ignore largely the unique properties of ENS and apply mechanically the hypotheses formed in CNS studies to ENS researches. In this review, the structure and function of ENS are briefly introduced, and the importance of extraordinary characteristics of ENS is illustrated by the problems encountered in our studies.

A artrite reumatoide afeta o sistema nervoso entérico? / Does the rheumatoid arthritis affect the enteric nervous system?

ABSTRACT BACKGROUND: Few studies regarding arthritic diseases have been performed to verify the presence of the neurodegeneration. Given the increased oxidative stress and extra-articular effects of the rheumatoid arthritis, the gastrointestinal studies should be further investigated aiming a better understanding of the systemic effects the disease on enteric nervous system. OBJECTIVE: To determine whether the rheumatoid arthritis affects the nitrergic density and somatic area of the nNOS- immunoreactive (IR) myenteric neurons, as well as the morphometric areas of CGRP and VIP-IR varicosities of the ileum of arthritic rats. METHODS: Twenty 58-day-old male Holtzmann rats were distributed in two groups: control and arthritic. The arthritic group received a single injection of the Freund's Complete Adjuvant in order to induce arthritis model. The whole-mount preparations of ileum were processed for immunohistochemistry to VIP, CGRP and nNOS. Quantification was used for the nitrergic neurons and morphometric analyses were performed for the three markers. RESULTS: The arthritic disease induced a reduction 6% in ileal area compared to control group. No significant differences were observed in nitrergic density comparing both groups. However, arthritic group yielded a reduction of the nitrergic neuronal somatic area and VIP-IR varicosity areas. However, an increase of varicosity CGRP-IR areas was also observed. CONCLUSION: Despite arthritis resulted in no alterations in the number of nitrergic neurons, the retraction of ileal area and reduction of nitrergic somatic and VIP-IR varicosity areas may suggest a negative impact the disease on the ENS.

RESUMO CONTEXTO: Poucos estudos sobre doenças artríticas têm sido realizados para verificar a presença de neurodegeneração. Diante do aumento do estresse oxidativo e dos efeitos extra-articulares da artrite reumatoide, estudos gastrointestinais devem ser investigados visando uma melhor compreensão dos efeitos sistêmicos da doença no sistema nervoso entérico. OBJETIVO: Determinar se a artrite reumatoide afeta a densidade nitrérgica e a área somática dos neurônios mioentéricos imunorreativos ao nNOS (nNOS-IR), bem como para as áreas morfométricas das varicosidades CGRP-IR e VIP-IR do íleo de ratos artríticos. MÉTODOS: Vinte ratos Holtzmann, com 58 dias de idade, foram distribuídos em dois grupos: controle e artrítico. O grupo artrítico recebeu uma única injeção do adjuvante completo de Freund para induzir o modelo de artrite. Os preparados totais de íleo foram processados para imuno-histoquímica ao VIP, CGRP e nNOS. A quantificação foi utilizada para os neurônios nitrérgicos e as análises morfométricas foram realizadas para os três marcadores. RESULTADOS: A doença artrítica induziu uma redução de 6% na área ileal em relação ao grupo controle. Não foram observadas diferenças significativas na densidade nitrérgica comparando os dois grupos. No entanto, o grupo artrítico produziu uma redução da área somática neuronal nitrérgica e da área das varicosidades do VIP-IR. Entretanto, foi observado um aumento das áreas das viricosidades CGRP-IR. CONCLUSÃO: Apesar da artrite não resultar em alterações no número de neurônios nitrérgicos, a retração da área ileal e a redução das áreas somática nitrérgica e das varicosidades do VIP-IR podem sugerir um impacto negativo da doença no sistema nervoso entérico.

Pyridostigmine in Pediatric Intestinal Pseudo-obstruction: Case Report of a 2-year Old Girl and Literature Review

Pediatric chronic intestinal pseudo-obstruction is a rare disorder characterized by a severe impairment of gastrointestinal motility leading to intestinal obstruction symptoms in the absence of mechanical causes. The diagnosis is usually clinical and diagnostic work is usually aimed to rule out mechanical obstruction and to identify any underlying diseases. Treatment is challenging and requires a multidisciplinary effort. In this manuscript we describe the youngest child successfully treated with the orally administrable, long-acting, reversible anti-cholinesterase drug, pyridostigmine. Like other drugs belonging to cholinesterase inhibitors, pyridostigmine enhances gut motility by increasing acetylcholine availability in the enteric nervous system and neuro-muscular junctions. Based on the direct evidence from the reported case, we reviewed the current literature on the use of pyridostigmine in severe pediatric dysmotility focusing on intestinal pseudo-obstruction. The overall data emerged from the few published studies suggest that pyridostigmine is an effective and usually well tolerated therapeutic options for patients with intestinal pseudo-obstruction. More specifically, the main results obtained by pyridostigmine included marked reduction of abdominal distension, reduced need of parenteral nutrition, and improvement of oral feeding. The present case and review on pyridostigmine pave the way for eagerly awaited future randomized controlled studies testing the efficacy of cholinesterase inhibitors in pediatric severe gut dysmotility.

Parkinson's Disease: The Emerging Role of Gut Dysbiosis, Antibiotics, Probiotics, and Fecal Microbiota Transplantation

The role of the microbiome in health and human disease has emerged at the forefront of medicine in the 21st century. Over the last 2 decades evidence has emerged to suggest that inflammation-derived oxidative damage and cytokine induced toxicity may play a significant role in the neuronal damage associated with Parkinson's disease (PD). Presence of pro-inflammatory cytokines and T cell infiltration has been observed in the brain parenchyma of patients with PD. Furthermore, evidence for inflammatory changes has been reported in the enteric nervous system, the vagus nerve branches and glial cells. The presence of α-synuclein deposits in the post-mortem brain biopsy in patients with PD has further substantiated the role of inflammation in PD. It has been suggested that the α-synuclein misfolding might begin in the gut and spread “prion like” via the vagus nerve into lower brainstem and ultimately to the midbrain; this is known as the Braak hypothesis. It is noteworthy that the presence of gastrointestinal symptoms (constipation, dysphagia, and hypersalivation), altered gut microbiota and leaky gut have been observed in PD patients several years prior to the clinical onset of the disease. These clinical observations have been supported by in vitro studies in mice as well, demonstrating the role of genetic (α-synuclein overexpression) and environmental (gut dysbiosis) factors in the pathogenesis of PD. The restoration of the gut microbiome in patients with PD may alter the clinical progression of PD and this alteration can be accomplished by carefully designed studies using customized probiotics and fecal microbiota transplantation.

Altered Gut Microbiome and Intestinal Pathology in Parkinson's Disease

Parkinson's disease (PD) is a common neurodegenerative disorder arising from an interplay between genetic and environmental risk factors. Studies have suggested that the pathological hallmarks of intraneuronal α-synuclein aggregations may start from the olfactory bulb and the enteric nervous system of the gut and later propagate to the brain via the olfactory tract and the vagus nerve. This hypothesis correlates well with clinical symptoms, such as constipation, that may develop up to 20 years before the onset of PD motor symptoms. Recent interest in the gut–brain axis has led to vigorous research into the gastrointestinal pathology and gut microbiota changes in patients with PD. In this review, we provide current clinical and pathological evidence of gut involvement in PD by summarizing the changes in gut microbiota composition and gut inflammation associated with its pathogenesis.

Does Parkinson's disease start in the gut? / A doença de Parkinson começa no intestino?

ABSTRACT Current understanding of the pathophysiology of Parkinson's disease suggests a key role of the accumulation of alpha-synuclein in the pathogenesis. This critical review highlights major landmarks, hypotheses and controversies about the origin and progression of synucleinopathy in Parkinson's disease, leading to an updated review of evidence suggesting the enteric nervous system might be the starting point for the whole process. Although accumulating and compelling evidence favors this theory, the remaining knowledge gaps are important points for future studies.

RESUMO O atual entendimento sobre a fisiopatologia da doença de Parkinson (DP) sugere um papel central do acúmulo de alfa-sinucleína na patogenia da DP Esta revisão crítica revisita marcos, teorias e controvérsias a respeito da origem e progressão da sinucleinopatia, apresentando uma atualização das principais evidências sugerindo que o sistema nervoso entérico seria o local inicial deste processo. Apesar das evidências a favor desta teoria serem crescentes e instigantes, as lacunas de conhecimento a este respeito são importantes pontos para estudos futuros.

A Case of Duodenal Ganglioneuroma Manifesting as a Subepithelial Tumor

Ganglioneuroma of the gastrointestinal tract is a rare tumor that consists of ganglion cells, nerve fibers, and supporting cells of the enteric nervous system. Ganglioneuromas are usually associated with genetic disorders such as the multiple endocrine neoplasia syndrome or neurofibromatosis. Ganglioneuromas of the gastrointestinal tract predominantly involve the colon and rectum, and reports about duodenal ganglioneuromas are few. Herein, we report a case of duodenal ganglioneuroma treated with endoscopic resection. A 56-year-old female patient visited our hospital because of a subepithelial tumor in the second portion of the duodenum. She had no remarkable medical or family history and revealed no history of genetic disorders. Endoscopic ultrasonography and abdominal computed tomography revealed a tumor located mainly in the submucosal layer, without any regional lymph node involvement. Endoscopic resection of the lesion was performed, and the pathological examination confirmed a duodenal ganglioneuroma.

Relation of Enteric α-Synuclein to Gastrointestinal Dysfunction in Patients With Parkinson's Disease and in Neurologically Intact Subjects

BACKGROUND/AIMS: α-Synucleinopathy in the brain is the neuropathological hallmark of Parkinson’s disease (PD). However, the functional impact of α-synucleinopathy in the enteric nervous system remains unknown. We aim to evaluate the association between gastrointestinal (GI) dysfunction and α-synuclein (αSYN) pathology in the stomach and colon of PD patients and controls, as well as to investigate the association between the αSYN pathology in GI tract and future PD risk. METHODS: A total of 35 PD patients and 52 neurologically intact subjects were enrolled in this study. Endoscopic biopsies were performed, and then immunohistochemical staining for αSYN was performed. All subjects completed the validated Rome III questionnaire for the assessment of GI symptoms. The association between GI symptoms and the αSYN pathology in GI mucosa was evaluated. Incident PD cases were assessed during a median follow-up of 46 months. RESULTS: The proportion of self-reported constipation and functional constipation through the Rome III questionnaire was significantly higher in PD patients than in controls (P 0.05). No incident PD cases were diagnosed during study period. CONCLUSIONS: Our present study suggests that the deposition of αSYN in the mucosal enteric nervous system may not be reflected by functional impairment of the affected segment of the gut.

Enteric pathogen co-infections in the paediatric population from rural communities in the Vhembe District, South Africa

Background. Enteric pathogens co-infections are a serious health risk in children under the age of 5 years.Objective. The study aimed to determine the prevalence of diarrhoea-causing pathogens in children suffering from diarrhoea in rural communities of the Vhembe District.Methods. A cross-sectional study was conducted from July 2014 to June 2015. Diarrhoeal stool specimens (N=237) were collected from children attending primary healthcare facilities in rural communities of the Vhembe District. Stools were screened for enteric viral adenovirus 40/41, rotavirus and norovirus pathogens by means of enzyme immuno-assay (EIA) and enteric bacterial Escherichia coli spp.(diarrhoeagenic pathotypes), Shigella spp., Salmonella spp. and Vibrio spp. pathogens by means of multiplex polymerase chain reaction.Results. A total of 59.1% (140/237) were positive for at least one or more enteric pathogens.Enterotoxigenic E. coli (ETEC) (27.9%),enteroaggregative E. coli (EAEC) (26.8%) and atypical enteropathogenic E. coli (EPEC) (17.9%) were frequently detected in children less than 2 years of age. Bacterial-bacteria co-infections were detected in 24.5% (n=58) and bacterial-viral co-infections in 14.3% (n=34) of the stool specimens.Conclusion. The findings indicated that enteric pathogen co-infections are major causes of diarrhoea in children less than 2 years of age in the Vhembe District

Experimental study of neural plasticity in chagasic megacolon in rats

This is a cross-sectional and experimental study. The purpose of the study was to measure enteric neurons in rats with chagasic megacolon. Twenty-three male rats inoculated with 1,500,000 trypomastigotes of the Y strain of Trypanosoma cruzi were used. The animals were sedated intramuscularly at zero inoculation time (T0 ) and at sixty days after inoculation (T60), to perform a barium enema test to evaluate the dilatation of the different segments of the colon. Evidence of infection was performed with a blood smear collected from the animals' tails 18 days after inoculation with observation of blood forms. Membrane preparations underwent dual-label immunofluorescence of global and nitrergic neurons with HuC / HuD antibody and nNOS antibody, respectively. Subsequently, quantitative and morphometric analysis of cecal and proximal colon segments were performed. In the quantitative analysis of the proximal colon segment there was a significant decrease in the numbers of total neurons (Hucolo p=0.001), as well as in the number of nitrergic neurons (NOScolo p=0.032) in the population of rats with chagasic megacolon in relation to the control group. In the cecal segment, this difference was not observed in the result of the total neuron counts (Huceco p=0.289) and nitrergic neurons (NOSececo p=0.466). In the morphometric analysis, considering only the cell body area, a significant difference in the size of the neurons with p=0.000 was observed in the cecal segment. The extensive loss of total neurons that cause predominance of nitrergic neurons contributes to the development of megacolon and neuronal volume increase in the cholinergic neurons, this plasticity does not reestablish the lost equilibrium, causing megacolon.

Gastroparesis Updates on Pathogenesis and Management

Gastroparesis (Gp) is a chronic disease that presents with clinical symptoms of early satiety, bloating, nausea, vomiting, and abdominal pain. Along with these symptoms, an objective finding of delayed gastric emptying, along with a documented absence of gastric outlet obstruction, are required for diagnosis. This article focuses on updates in the pathogenesis and management of Gp. Recent studies on full thickness biopsies of Gp patients have shed light on the complex interactions of the central, autonomic, and enteric nervous systems, which all play key roles in maintaining normal gut motility. The management of Gp has evolved beyond prokinetics and antiemetics with the use of gastric electrical stimulators (GES). In addition, this review aims to introduce the concept of gastroparesis-like syndrome (GLS). GLS helps groups of patients who have the cardinal symptoms of Gp but have a normal or rapid emptying test. Recent tests have shown that patients with Gp and GLS have similar pathophysiology, benefit greatly from GES placement, and likely should be treated in a similar manner.

Gastroparesis Updates on Pathogenesis and Management

Gastroparesis (Gp) is a chronic disease that presents with clinical symptoms of early satiety, bloating, nausea, vomiting, and abdominal pain. Along with these symptoms, an objective finding of delayed gastric emptying, along with a documented absence of gastric outlet obstruction, are required for diagnosis. This article focuses on updates in the pathogenesis and management of Gp. Recent studies on full thickness biopsies of Gp patients have shed light on the complex interactions of the central, autonomic, and enteric nervous systems, which all play key roles in maintaining normal gut motility. The management of Gp has evolved beyond prokinetics and antiemetics with the use of gastric electrical stimulators (GES). In addition, this review aims to introduce the concept of gastroparesis-like syndrome (GLS). GLS helps groups of patients who have the cardinal symptoms of Gp but have a normal or rapid emptying test. Recent tests have shown that patients with Gp and GLS have similar pathophysiology, benefit greatly from GES placement, and likely should be treated in a similar manner.

Slow Wave Activity and Modulations in Mouse Jejunum Myenteric Plexus In Situ

BACKGROUND/AIMS: Myenteric plexus interstitial cells of Cajal (ICC-MY) are involved in the generation of gut pacemaker activity and neuronal communication. We performed patch clamp on ICC-MY in situ to observe the changes of pacemaker activity in response to neural modulations. METHODS: A fresh longitudinal muscle with myenteric plexus (LMMP) from mouse jejunum was prepared. ICC-MY and ganglion neurons embedded in the layer of longitudinal muscles were targeted by patch clamping in whole-cell configuration in a model of current or voltage clamp. Neurogenic modulators were applied to evaluate their effects on ICC pacemaker activity. RESULTS: In situ ICC-MY showed spontaneous and rhythmical voltage oscillations with a frequency of 27.2 ± 3.9 cycles/min, amplitude of 32.6 ± 6.3 mV, and resting membrane potential of −62.2 ± 2.8 mV. In situ neurons showed electrically evocable action potential in single or multiple spikes. Pacemaker activity was modulated by neuronal activators through receiving a neuronal input. Application of tetrodotoxin depolarized pacemaker potentials in a dose dependent manner, and decreased the amplitude at tetrodotoxin 0.3 μM for about 40 ± 10%; capsaicin (1 μM) ameliorated ICC-MY K+ current for about 49 ± 14.8%; and, nitric oxide hyperpolarized pacemaker potential and decreased the amplitude and frequency. CONCLUSIONS: The in situ preparation patch clamp study further demonstrates that the pacemaker activity is an intrinsic property of ICC. The neurogenic activators change and shape pacemaker potential and activity in situ. LMMP preparation in situ patch clamp provides an ideal platform to study the functional innervation of the ICC and the enteric neural system, thereby, for evaluating the neural regulation of pacemaker activity, especially in disorder models.

Morphoquantitative study of Rattus norvegicus submucosal plexus by different neuronal evidentiation histochemical techniques / Estudio morfocuantitativo del plexo submucoso de Rattus norvegicus por medio de diferentes técnicas histoquímicas para verificar características neuronales

Enteric nervous plexuses have been the object of several studies, specially the myenteric plexus whose studies describe its organization, functions and alterations. On the other hand, the submucosal plexus has been less studied and still needs descriptive studies. To analyze morphologically and quantitatively submucosal neurons of the jejunum of 90-day-old healthy rats using different techniques for neuronal staining as a way to provide normality data to compare with future experimental studies. Whole mount preparations of the jejunum were submitted to Giemsa, NADH-diaphorase and NADPH-diaphorase techniques to stain the total neuronal population, more metabolically active subpopulation and subpopulation of nitrergic neurons, respectively. Neurons of the submucosal plexus of adult rats are mainly organized in ganglia with varied sized and shapes. Giemsa technique stained 243.93 ± 7.68 neurons per mm2. Regarding the total population stained by Giemsa, NADH- diaphorase positive (139.09 ± 11.14/mm2) neurons represented 57 % and NADPH-diaphorase positive (18.17 ± 0.28/mm2) represented 7.5 %. The area of the cell body was bigger in nitrergic neurons (412.29 ± 150.22) than in the ones stained by Giemsa (254.71 ± 63.32) and NADH-diaphorase positive (243.98 ± 123.82).

El plexo nervioso entérico ha sido objeto de varios estudios, especialmente el plexo mientérico, cuyos estudios consisten en describir su organización, funciones y alteraciones. Por otro lado, el plexo submucoso ha sido menos investigado y todavía necesita estudios descriptivos. Para analizar morfológica y cuantitativamente las neuronas de la submucosa del yeyuno de ratas de 90 días de edad, se realizaron diferentes técnicas de tinción neuronales, en animales sanos, como una forma de proporcionar datos de normalidad y compararlo con futuros estudios experimentales. Se realizaron montajes con preparados enteros del yeyuno que fueron sometidos a las técnicas de Giemsa, de NADPH-diaforasa y NADH-diaforasa para teñir la población total neuronal, subpoblación más activa metabólicamente y subpoblación de neuronas nitrérgicas, respectivamente. Las neuronas del plexo submucoso de ratas adultas se organizan principalmente en los ganglios con variaciones de tamaño y formas. Con la técnica de Giemsa se tiñeron 243.93±7.68 neuronas por mm2. Con respecto a la población total teñida con Giemsa, fueron positivas para NADH- diaforasa en 139.09 ±11.14 / mm2 neuronas, representando el 57% y fueron positivas para NADPH-diaforasa en 18,17 ± 0,28 / mm2 neuronas, lo que representó el 7,5%. El área del cuerpo celular fue mayor en neuronas nitrérgicas (412,29 ± 150.22) que en las teñidas con Giemsa (254,71 ± 63,32) y NADH-diaforasa positivas (243,98 ± 123,82).

Papel da via S100B/RAGE/NFkB na patogênese da mucosite intestinal experimental por 5-fluorouracil desregulação de células gliais e de neurônios entéricos

5-Fluorouracil (5-FU) promotesintestinal mucositis and motility alterations. Themucositis affect about40% of patients receiving 5-FU and there arereports of patients presentingmucositis afterthe first dose. Under other inflammatory conditions, the S100βprotein is involved in the RAGE activation with subsequent NFκBtranslocation to the nucleus and transcription of TNF-αand iNOS. The enteric glial cells through several mediators, such asS100β, interact with the intestinal epithelial cells and enteric neurons. Therefore, the aim of this study was investigatethe effect of 5-FU in the enteric glial cells and neurons, as well as studythe role of the via S100β/RAGE/NFκB in the pathogenesis of the experimental intestinal mucositis. Swiss male mice received saline (control, 0.9%, i.p.) or5-FU (450 mg/Kg, i.p., single dose). After24h, mice weretreated with pentamidine, aS100 βinhibitor (P0.8 mg/Kg +5FU; P4 mg/Kg +5FU; or onlyP4mg/Kg, i.p.) during two days and euthanized on the fouth day of the experimental protocol...

O 5-Fluorouracil (5-FU) promove mucosite intestinal e alterações da motilidade.A mucositeatinge cerca de 40% dos pacientes em tratamento com5-FUe há relatos de pacientes que a apresentam na primeira dose administrada.Em outras condições inflamatórias, a proteína S100β está envolvida na ativação de RAGE com consequente translocação de NFκB para o núcleo e transcrição de TNF-αe de iNOS.As células gliais entéricas por meio deS100β,interagem com as células epiteliais intestinais e com os neurônios entéricos.Nesse contexto, oobjetivodeste estudo éinvestigar o efeito do5-FU nas células gliais e nos neurôniosentéricos, bem como estudar o papel da via S100β/RAGE/NFκB na patogênese da mucosite intestinal induzida por esse quimioterápico. Os camundongos Swiss machos receberam salina (0,9%, i.p.) ou 5-FU (450 mg/Kg, i.p. dose única). Após 24h da administração do quimioterápico, administrou-se pentamidina, inibidor de S100β (P0,8 mg/Kg +5FU; P4 mg/Kg +5FU; ou somente P4mg/Kg, i.p.) durante dois dias e os animais foram eutanasiadosno quarto dia do protocolo experimental...