Isolation and Purification of Chromaffin Granules from Adrenal Glands and Cultured Neuroendocrine Cells.

Chromaffin granules isolated from adrenal glands constitute a powerful experimental tool to the study of secretory vesicle components and their participation in fusion and docking processes, vesicle aggregation, and interactions with cytosolic components. Although it is possible to isolate and purify chromaffin granules from adrenal glands of different species, bovine adrenal glands are the most used tissue source due to its easy handling and the large amount of granules that can be obtained from this tissue. In this chapter, we describe an easy-to-use and short-term protocol for efficiently obtaining highly purified chromaffin granules from bovine adrenal medulla. We additionally include protocols to isolate granules from cultured bovine chromaffin cells and PC12 cells, as well as a section to obtain chromaffin granules from mouse adrenal glands.

Taquipnea persistente como manifestación inicial de hiperplasia de células neuroendocrinas: reporte de un caso clínico / Persistent tachypnea as initial manifestation of hyperplasia of neuroendocrine cells: case report

Se realiza revisión de la literatura y presentación de un caso clínico de Hiperplasia de Células Neuroendocrinas en paciente lactante masculino que inicia su padecimiento a los 3 meses de vida con dificultad respiratoria caracterizada por retracciones subcostales y taquipnea persistente, posterior-mente a los 8 meses de edad se agrega hipoxemia respirando aire ambiente que requiere uso de oxígeno suplementario continuo. Tiene antecedente de tres hospitalizaciones, con diagnóstico de Bronquiolitis y Neumonía atípica, realizándose panel viral respiratorio con reporte negativo. El paciente persiste con sintomatología respiratoria a pesar de tratamientos médicos, por lo que se deriva a neumología pediátrica, unidad de enfermedad pulmonar intersticial del lactante, iniciando protocolo de estudio, se realiza tomografía tórax de alta resolución, que evidencia imágenes en vidrio despulido en lóbulo medio y región lingular, además de atrapamiento aéreo. Se concluye el diagnóstico de Hiperplasia de Células neuroendocrinas con base a la clínica y hallazgos tomográficos. La Hiperplasia de Células Neuroendocrinas es una patología pulmonar intersticial poco frecuente, cuyo diagnóstico es clínico y radiológico, en la minoría de los casos se requiere biopsia pulmonar para confirmación. Puede ser fácilmente confundida con otras enfermedades respiratorias comunes, por lo que es importante sospecharla para realizar un diagnóstico precoz. La mayor parte de los casos evolucionan con declinación de los síntomas, mejorando espontáneamente en los primeros años de vida.

A review of the literature and presentation of a clinical case of Neuroendocrine Cell Hyperplasia in a male infant patient who begins his condition at 3 months of age with respiratory distress characterized by subcostal retractions and persistent tachypnea is presented. After 8 months of age hypoxemia is added requiring continuous oxygen therapy. He has a history of three hospitalizations, with a diagnosis of bronchiolitis and atypical pneumonia, respiratory viral panel has a negative report. The patient persists with respiratory symptoms despite medical treatments, so it is referred to pediatric pulmonology, initiating study protocol for interstitial lung disease of the infant. A high resolution chest tomography is performed, which evidences images in polished glass in the middle lobe and lingular region, in addition to air entrapment. The diagnosis of neuroendocrine cell hyperplasia is concluded based on clinical and tomographic findings. Neuroendocrine Cell Hyperplasia is a rare interstitial pulmonary pathology, whose diagnosis is clinical and radiological. Lung biopsy is required only in the minority of cases for confirming diagnosis. It can be easily confused with other common respiratory diseases, so it is important to suspect it to make an early diagnosis. Most cases evolve with decline in symptoms, improving spontaneously in the first years of life.

[Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia/tumorlets]. / Hiperplasia difusa idiopática de células neuroendocrinas pulmonares/tumorlets.

Diffuse idiopathic hyperplasia of neuroendocrine cells is an extremely rare condition. It is a widespread proliferation of neuroendocrine cells, without primary process justifying it. Usually symptomatic in most cases, asymptomatic forms are also described. We describe three cases, 2 women and 1 man, average age 63 years (range 57-71) who presented with bilateral pulmonary nodules. Average follow-up: one year and three months (range 1 month-3 years). The two women had cough, progressive dyspnea and airflow obstruction in the spirometry, and were treated for asthma and chronic obstructive pulmonary disease, respectively, with little relief of symptoms. The remaining patient consulted for diagnosis of pulmonary nodules of unknown cause and a suspicion of metastatic disease. The biopsies diagnostic were: in the first and third case diffuse idiopathic hyperplasia of euroendocrine cells - tumorlets; and in the second case typical carcinoid tumor and diffuse idiopathic hyperplasia of neuroendocrine cells. The first patient controlled the symptoms with maximum bronchodilator therapy. The second patient presented immediate postoperative severe bronchospasm and respiratory failure which required ventilatory assistance, atrial fibrillation with rapid ventricular response (both signs interpreted as paraneoplastic syndromes) which responded favorably to the empirical octeotride management. The third patient is asymptomatic and in control. The diffuse neuroendocrine cell hyperplasia represents a diagnostic challenge because of the rarity of this condition. Lung biopsy in patients with multiple, bilateral pulmonary nodules and clinical history of cough and progressive dyspnea should be considered to confirm this entity.

La hiperplasia difusa idiopática de células neuroendocrinas es una entidad extremadamente infrecuente caracterizada por una proliferación generalizada de células neuroendocrinas, sin proceso primario que lo justifique, generalmente, aunque también están descriptas formas asintomáticas. Se describen los casos de dos mujeres y un hombre, edad promedio 63 años (rango 57-71) que consultaron por presentar nodulillos pulmonares bilaterales. Promedio de seguimiento: 1 año, 3 meses (rango 1 mes-3 años). Las dos mujeres presentaban tos, disnea progresiva y obstrucción al flujo aéreo en el estudio espirométrico, fueron tratadas por asma y enfermedad pulmonar obstructiva crónica respectivamente con poco alivio de los síntomas. El tercer paciente, varón, consultó por hallazgo incidental en una tomografía de tórax, de nódulos pulmonares, con razonable sospecha de enfermedad metastásica de origen desconocido. En sendas biopsias se diagnosticaron: en el primer y tercer caso hiperplasia neuroendócrina difusa idiopática-tumorlets; y en el segundo caso tumor carcinoide típico e hiperplasia neuroendocrina difusa idiopática. En el primer caso los síntomas se controlaron con tratamiento broncodilatador máximo. La segunda paciente tuvo en el postoperatorio, insuficiencia respiratoria que requirió asistencia respiratoria mecánica y fibrilación auricular con alta respuesta ventricular, interpretados ambos signos como síndromes paraneoplásicos, que respondieron favorablemente a la administración empírica de octeotride. El tercer paciente se halla asintomático y en control. La hiperplasia difusa de células neuroendócrinas representa un desafío diagnóstico. La biopsia pulmonar en pacientes con nodulillos pulmonares múltiples, bilaterales e historia clínica de tos y disnea progresiva debe ser considerada para confirmar esta entidad.

Taquipnea persistente de la infancia: hiperplasia de células neuroendocrinas, una revisión / Persistent tachypnea of infancy: neuroendocrine cell hyperplasia, a review

La hiperplasia de células neuroendocrinas de la infancia (HCNEI) constituye una de las enfermedades intersticiales más frecuentes en pediatría. Tanto su etiología como los mecanismos fisiopatológicos involucrados son inciertos. Suele presentarse en pacientes por lo demás sanos, durante los primeros meses de vida con taquipnea, retracciones costales, rales e hipoxemia. En la tomografía axial computada de tórax de alta resolución (TACAR) presenta imágenes características en vidrio esmerilado de distribución central y zonas de atrapamiento aéreo. Para el diagnóstico, además de la clínica y la TACAR, podemos recurrir a la biopsia en casos atípicos. Los hallazgos histológicos reflejan una arquitectura pulmonar normal y un aumento en el número de células neuroendocrinas. El manejo global es con medidas de sostén, ya que no se cuenta con un tratamiento específico. La sintomatología suele mejorar con la edad y el pronóstico es favorable.

Neuroendocrine cell hyperplasia of infancy (NEHI) is one of the most common interstitial lung diseases of childhood. The etiology and pathophysiological mechanisms involved are uncertain. It usually presents in otherwise healthy patients during the first months of life with tachypnea, rib retractions, crackles, and hypoxemia. High-resolution chest computed tomography (HRCT) shows ground-glass opacities of central distribution and areas of air trapping. For diagnosis purposes, in addition to clinical and HRCT features, a lung biopsy is indicated for atypical cases. Histological findings reflect normal architecture and an increased number of neuroendocrine cells. The management consists of supportive and preventive care, since there is no specific treatment. Symptoms usually improve with age and the prognosis is favorable.

Neuroendocrine Mechanisms Underlying Non-breeding Aggression: Common Strategies Between Birds and Fish.

Aggression is an adaptive behavior that plays an important role in gaining access to limited resources. Aggression may occur uncoupled from reproduction, thus offering a valuable context to further understand its neural and hormonal regulation. This review focuses on the contributions from song sparrows (Melospiza melodia) and the weakly electric banded knifefish (Gymnotus omarorum). Together, these models offer clues about the underlying mechanisms of non-breeding aggression, especially the potential roles of neuropeptide Y (NPY) and brain-derived estrogens. The orexigenic NPY is well-conserved between birds and teleost fish, increases in response to low food intake, and influences sex steroid synthesis. In non-breeding M. melodia, NPY increases in the social behavior network, and NPY-Y1 receptor expression is upregulated in response to a territorial challenge. In G. omarorum, NPY is upregulated in the preoptic area of dominant, but not subordinate, individuals. We hypothesize that NPY may signal a seasonal decrease in food availability and promote non-breeding aggression. In both animal models, non-breeding aggression is estrogen-dependent but gonad-independent. In non-breeding M. melodia, neurosteroid synthesis rapidly increases in response to a territorial challenge. In G. omarorum, brain aromatase is upregulated in dominant but not subordinate fish. In both species, the dramatic decrease in food availability in the non-breeding season may promote non-breeding aggression, via changes in NPY and/or neurosteroid signaling.

Clinical, functional, and computed tomography findings in a cohort of patients with neuroendocrine cell hyperplasia of infancy.

INTRODUCTION: Neuroendocrine cell hyperplasia of infancy (NEHI) is one of the most common interstitial lung diseases in children. Both the etiology and pathophysiological mechanisms of the disease are still unknown. Prognosis is usually favorable; however, there are significant morbidities during the early years of life. OBJECTIVE: To describe the clinical course, infant pulmonary function tests and computed tomography (CT) findings in a cohort of patients with NEHI in Argentina. METHODS: This is a observational multicenter cohort study of children diagnosed with NEHI between 2011 and 2020. RESULTS: Twenty patients participated in this study. The median age of onset of symptoms was 3 months and the median age at diagnosis was 6 months. The most common clinical presentation was tachypnea, retractions and hypoxemia. The chest CT findings showed central ground glass opacities and air trapping. Infant pulmonary function tests revealed an obstructive pattern in 75% of the cases (10/12). Most patients (75%) required home oxygen therapy for 17 months (interquartile range 12-25). In 85% of them, tachypnea and hypoxemia spontaneously resolved between the second and third years of life. CONCLUSION: In this cohort, the first symptoms appeared during the early months of life. The typical clinical, CT, and functional findings allowed the diagnosis without the need of a lung biopsy. Although most patients required home oxygen therapy, they showed a favorable evolution.

Neural crest derivatives and neuroendocrine cells in the gut of anencephalic and fetuses without congenital defects.

BACKGROUND: The enteric nervous system (ENS), a component of the peripheral nervous system in the intestinal walls, regulates motility, secretion, absorption, and blood flow. Neural crest (NC) migration, fundamental for ENS development, may be altered by central nervous system development alterations, such as neural tube defects (NTD). Intestinal innervation anomalies have been correlated to NTD. We aim to describe the ENS on a fetus with NTD and fetuses without congenital defects (FWCD). CASES: Two male and four female FWCD, 18-20 weeks-gestation (WG), and a 25 WG female anencephalic fetus. Samples from the pancreatoduodenal groove, jejunum, cecum, rectum, and appendix were analyzed by immunohistochemistry. Nervous plexuses were marked with Neuron-specific enolase and S-100; enteric glial cells with CD56; neuroendocrine cells with chromogranin and synaptophysin, and interstitial cells of Cajal (ICC) with CD117. RESULTS AND CONCLUSION: The anencephalic fetus presented a rudimentary brainstem with a cerebellum. Partial frontal, temporal, and occipital bones were found. A large atrial septal defect, an enlarged kidney with a duplex collecting system and a single adrenal gland were found. NSE, S100, and CD56, showed the presence of the myenteric and submucous plexuses of the ENS; scarce interplexus reactivity may indicate inadequate development. Pancreatic and gut neuroendocrine cells, identified with chromogranin and CD56, showed that the enteroendocrine system is present. Findings on FWCD using these markers are consistent with literature descriptions. Vagal NC migration appears to be unaffected despite the presence of anencephaly, although maturation of the ENS may be altered.

Hiperplasia de células neuroendocrinas: reporte de caso / Neuroendocrine cell hyperplasia: case report

A clinical case of Neuroendocrine Cell Hyperplasia is presented with a bibliographic review. An infant patient with respiratory distress syndrome, characterized by nasal flaring, retractions, and tachypnea with temporary resolution with the use of bronchodilators. However, the patient requires oxygen. With complementary examinations (negative viral panel twice) and epidemiology it is classified as a viral Bronchiolitis. Without improvement, extrapulmonar pathologies were suspected, discarding hearth disease, epilepsy, pathological gastroesophageal reflux. New tests were performed to rule out other pathologies, including immunological disorders. Those results were normal, so a high-resolution chest tomography was done which allowed the diagnosis of Neuroendocrine Cell Hyperplasia. During the follow up the child had improved and required oxygen until he was two years old. Neuroendocrine Cell Hyperplasia belongs to a huge group of less common interstitial disorders, which diagnosis is clinical and radiological. It can easily be confused with common respiratory disorders. For this reason, it is important to know about this disease to make an early diagnosis. Most of the cases had a gradual (months to years) improvement.

Se presenta un caso clínico de Hiperplasia de Células Neuroendocrinas y la revisión de la literatura. Paciente lactante menor con cuadro de dificultad respiratoria, caracterizado por aleteo nasal, retracciones y taquipnea persistente acompañada de desaturación. Sin adecuada respuesta al uso de broncodilatadores. Por exámenes complementarios, panel viral negativo en dos ocasiones y epidemiología, se le diagnostica una bronquiolitis viral. Por no presentar mejoría se completan estudios, descartándose neumonía atípica, cardiopatía, epilepsia, reflujo gastroesofágico patológico y compromiso inmunológico. El diagnóstico fue determinado en base a la clínica, junto con imágenes en vidrio esmerilado característicos en lóbulo medio y língula. En su seguimiento mejora paulatinamente, requiriendo soporte de oxígeno hasta los dos años. La Hiperplasia de Células Neuroendocrinas es una patología intersticial pulmonar poco frecuente, cuyo diagnóstico es clínico y radiológico. Puede ser fácilmente confundida con desórdenes respiratorios comunes, por lo que es importante sospecharla para realizar un diagnóstico precoz. La mayor parte de los casos evolucionan con declinación de los síntomas, mejorando espontáneamente en meses o en los primeros años de vida.

Hiperplasia de células neuroendocrinas que simula tumor sólido de páncreas / Neuroendocrine cell hyperplasia mimicking a solid pancreatic tumor

RESUMEN La hiperplasia de células neuroendocrinas pancreáticas es una patología donde se produce un aumen to en el número de células de los islotes de Langerhans y a veces puede simular un proceso tumoral. Caso clínico: presentamos el caso de un paciente con tumor sólido de cola de páncreas, sintomático, al que se le realizó esplenopancreatectomía corporocaudal laparoscópica. El resultado anatomopatoló gico posterior informó una hiperplasia neuroendocrina. Conclusión: la hiperplasia de células neuroen docrinas debería considerarse en el diagnóstico diferencial de tumores sólidos de páncreas. La alterna tiva quirúrgica laparoscópica es factible cuando no es posible establecer el diagnóstico prequirúrgico con estudios de imágenes o biopsia.

ABSTRACT Pancreatic endocrine cell hyperplasia is defined as an increase in the number of cells of Langerhans islets and can sometimes mimic a tumoral process. Case report: a male patient with a symptomatic solid tail of pancreas tumor underwent laparoscopic distal pancreatectomy and splenectomy. The pathological examination reported neuroendocrine cell hyperplasia. Conclusion: pancreatic endocrine cell hyperplasia should be considered in the differential diagnosis of solid pancreatic tumors. Laparoscopic surgery is feasible when the preoperative diagnosis with imaging tests of biopsy is not possible.

The Expression of Hormone Receptors as a Gateway toward Understanding Endocrine Actions in Female Pelvic Floor Muscles.

OBJECTIVE: To provide an overview of the hormone actions and receptors expressed in the female pelvic floor muscles, relevant for understanding the pelvic floor disorders. METHODS: We performed a literature review focused on the expression of hormone receptors mainly in the pelvic floor muscles of women and female rats and rabbits. RESULTS: The impairment of the pelvic floor muscles can lead to the onset of pelvic floor dysfunctions, including stress urinary incontinence in women. Hormone milieu is associated with the structure and function alterations of pelvic floor muscles, a notion supported by the fact that these muscles express different hormone receptors. Nuclear receptors, such as steroid receptors, are up till now the most investigated. The present review accounts for the limited studies conducted to elucidate the expression of hormone receptors in pelvic floor muscles in females. CONCLUSION: Hormone receptor expression is the cornerstone in some hormone-based therapies, which require further detailed studies on the distribution of receptors in particular pelvic floor muscles, as well as their association with muscle effectors, involved in the alterations relevant for understanding pelvic floor disorders.

Immune-neuroendocrine and metabolic disorders in human and experimental T. cruzi infection: New clues for understanding Chagas disease pathology.

Studies in mice undergoing acute Trypanosoma cruzi infection and patients with Chagas disease, led to identify several immune-neuroendocrine disturbances and metabolic disorders. Here, we review relevant findings concerning such abnormalities and discuss their possible influence on disease physiopathology.

Hiperplasia neuroendocrina en colitis linfocitica y colitis ulcerativa / Neuroendocrine hiperplasia in linfocitic and ulcerative colitis

Introducción: Algunos autores han demostrado incremento de células neuroendócrinas en colitis microscópica y colitis ulcerativa. Objetivo: El objetivo del presente estudio fue evaluar la presencia de células neuroendócrinas en colitis linfocítica, colitis colagenosa y colitis ulcerativa en comparación a controles. Materiales y métodos: Se usó inmunohistoquímica para identificar a las células neuroendócrinas a través del marcador cromogranina A. El estudio incluyó 10 casos de cada diagnóstico de colitis linfocítica, colitis colagenosa y colitis ulcerativa. Resultados: Se encontró diferencia estadísticamente significativa en el conteo de células neuroendocrinas en colitis linfocítica (p=0,019104) y colitis ulcerativa en comparación con los controles (p=0,0077). En colitis colagenosa, se encontró un incremento de células neuroendocrinas pero no pudimos demostrar diferencias estadísticamente significativa. Conclusión: Se demostró hiperplasia de células neuroendocrinas en colitis linfocítica y colitis ulcerativa, lo que confirma lo reportado por los pocos estudios anteriores realizados sobre el tema.

Introduction: Some authors have found increase of neuroendocrine cells in microscopic colitis and ulcerative colitis. Objective: The aim of this study is to evaluate the presence of neuroendocrine cells in ulcerative colitis and lymphocytic colitis and collagenous colitis. Materials and methods: Immunohistochemistry was performed to identify neuroendocrine cells through marker chromogranin A (CgA). The study included 10 cases of each diagnosis of Lymphocytic colitis, collagenous colitis and ulcerative colitis. Results: There was statistically significant difference in the count of neuroendocrine cells, between lymphocytic colitis and control (p=0.019104), and between ulcerative colitis and controls (p=0.0077). In collagenous colitis there was an increase in neuroendocrine cells but we failed to find statistical differences. Conclusion: We could observe neuroendocrine cell hyperplasia in lymphocytic colitis and ulcerative colitis compared with controls, which confirm previous studies.

Influence of pre-existing hypertension on neuroendocrine and cardiovascular changes evoked by chronic stress in female rats.

This study investigated neuroendocrine, autonomic, and cardiovascular changes evoked by daily exposure to the same type of stressor (homotypic) or different aversive stressor stimuli (heterotypic) in 60-days-old female normotensive Wistar rats and female spontaneously hypertensive rats (SHR). Both strains of rats were exposed for 10 consecutive days to either the homotypic stressor repeated restraint stress (RRS) or the heterotypic stressor chronic unpredictable stress (CUS). As expected, SHR had higher baseline blood pressure values and impaired baroreflex activity in relation to normotensive animals. Besides, SHR presented higher plasma corticosterone levels and decreased thymus weight. Both RRS and CUS increased baseline plasma corticosterone concentration and decreased body weight gain in both normotensive and SHR rats. In addition, both stress protocols caused hypertrophy of adrenal glands in normotensive rats. Regarding the cardiovascular effects, RRS increased basal heart rate in both rat strains, which was mediated by an increase in sympathetic tone to the heart. Besides, RRS increased baroreflex-mediated tachycardia in SHR animals, while CUS increased cardiac parasympathetic activity and pacemaker activity in normotensive rats. Taken together, these results indicate a stress type-specific effect, as identified by a vulnerability of both strains to the deleterious cardiovascular effects evoked by the homotypic stressor and a resilience to the impact of the heterotypic stressor. Vulnerability of hypertensive rats was evidenced by the absence of CUS-evoked adaptive cardiovascular responses and an increase of baroreflex tachycardia in SHR animals subjected to RRS. The somatic and HPA axis changes were overall independent of the chronic stress regimen and pre-existing hypertension.

GABA promotes gastrin-releasing peptide secretion in NE/NE-like cells: Contribution to prostate cancer progression.

In prostate cancer (PCa), neuroendocrine cells (NE) have been associated with the progression of the disease due to the secretion of neuropeptides that are capable of diffusing and influence surrounding cells. The GABAergic system is enriched in NE-like cells, and contributes to PCa progression. Additionally, γ-aminobutyric acid (GABA) stimulates the secretion of gastrin-releasing peptide (GRP) in peripheral organs. For the first time, in this study we show the role of GABA and GABAB receptor 1 (GABBR1) expression in GRP secretion in NE-like prostate cancer cells. We demonstrated an increase in GRP levels in NE-like cell medium treated with GABAB receptor agonist. Moreover, the blocking of this receptor inhibited GABA-induced GRP secretion. The invasive potential of PC3 cells was enhanced by either GRP or conditioned medium of NE-like cells treated with GABA. Additionally, we confirmed a positive correlation between GABA and GRP levels in the serum of PCa patients with NE markers. Finally, using public available data sets, we found a negative correlation between GABBR1 and androgen receptor (AR) expression, as well as a strong positive correlation between GABBR1 and enolase 2. These results suggest that GABA via GABBR1 induces GRP secretion in NE like cells involved in PCa progression.

[Neuroendocrine hiperplasia in linfocitic and ulcerative colitis]. / Hiperplasia neuroendocrina en colitis linfocitica y colitis ulcerativa.

INTRODUCTION: Some authors have found increase of neuroendocrine cells in microscopic colitis and ulcerative colitis. OBJECTIVE: The aim of this study is to evaluate the presence of neuroendocrine cells in ulcerative colitis and lymphocytic colitis and collagenous colitis. MATERIALS AND METHODS: Immunohistochemistry was performed to identify neuroendocrine cells through marker chromogranin A (CgA). The study included 10 cases of each diagnosis of Lymphocytic colitis, collagenous colitis and ulcerative colitis. RESULTS: There was statistically significant difference in the count of neuroendocrine cells, between lymphocytic colitis and control (p=0.019104), and between ulcerative colitis and controls (p=0.0077). In collagenous colitis there was an increase in neuroendocrine cells but we failed to find statistical differences. CONCLUSION: We could observe neuroendocrine cell hyperplasia in lymphocytic colitis and ulcerative colitis compared with controls, which confirm previous studies.

The pro-inflammatory cytokines IFNγ/TNFα increase chromogranin A-positive neuroendocrine cells in the colonic epithelium.

The gastrointestinal tract is the largest hormone-producing organ in the body due to a specialized cell population called enteroendocrine cells (EECs). The number of EECs increases in the mucosa of inflammatory bowel disease patients; however, the mechanisms responsible for these changes remain unknown. Here, we show that the pro-inflammatory cytokines interferon γ (IFNγ) and tumor necrosis factor α (TNFα) or dextran sulfate sodium (DSS)-induced colitis increase the number of EECs producing chromogranin A (CgA) in the colonic mucosa of C57BL/6J mice. CgA-positive cells were non-proliferating cells enriched with inactive phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and autophagy markers. Moreover, inhibition of Akt and autophagy prevented the increase in CgA-positive cells after IFNγ/TNFα treatment. Similarly, we observed that CgA-positive cells in the colonic mucosa of patients with colitis expressed Akt and autophagy markers. These findings suggest that Akt signaling and autophagy control differentiation of the intestinal EEC lineage during inflammation.

How the stimulus defines the dynamics of vesicle pool recruitment, fusion mode, and vesicle recycling in neuroendocrine cells.

The pattern of stimulation defines important characteristics of the secretory process in neurons and neuroendocrine cells, including the pool of secretory vesicles being recruited, the type and amount of transmitters released, the mode of membrane retrieval, and the mechanisms associated with vesicle replenishment. This review analyzes the mechanisms that regulate these processes in chromaffin cells, as well as in other neuroendocrine and neuronal models. A common factor in these mechanisms is the spatial and temporal distribution of the Ca(2+) signal generated during cell stimulation. For instance, neurosecretory cells and neurons have pools of vesicles with different locations with respect to Ca(2+) channels, and those pools are therefore differentially recruited following different patterns of stimulation. In this regard, a brief stimulus will induce the exocytosis of a small pool of vesicles that is highly coupled to voltage-dependent Ca(2+) channels, whereas longer or more intense stimulation will provoke a global Ca(2+) increase, promoting exocytosis irrespective of vesicle location. The pattern of stimulation, and therefore the characteristics of the Ca(2+) signal generated by the stimulus also influence the mode of exocytosis and the type of endocytosis. Indeed, low-frequency stimulation favors kiss-and-run exocytosis and clathrin-independent fast endocytosis, whereas higher frequencies promote full fusion and clathrin-dependent endocytosis. This latter type of endocytosis is accelerated at high-frequency stimulation. Synaptotagmins, calcineurin, dynamin, complexin, and actin remodeling, appear to be involved in the mechanisms that determine the response of these processes to Ca(2+) . In chromaffin cells, a brief stimulus induces the exocytosis of a small pool of vesicles that is highly coupled to voltage-dependent Ca(2+) channels (A), whereas longer or high-frequency stimulation provokes a global Ca(2+) increase, promoting exocytosis irrespective of vesicle location (B). Furthermore, low-frequency stimulation favors kiss-and-run exocytosis (A), whereas higher frequencies promote full fusion (B). In this review, we analyze the mechanisms by which a given stimulation pattern defines the mode of exocytosis, and recruitment and recycling of neurosecretory vesicles. This article is part of a mini review series on Chromaffin cells (ISCCB Meeting, 2015).

111In-Pentetreotide Imaging in Diffuse Idiopathic Neuroendocrine Hyperplasia of the Lung.

Diffuse idiopathic endocrine neoplasia of the lung (DIPNECH) is a rare disease characterized by proliferation of neuroendocrine cells in the bronchial wall. Less than 20 cases of DIPNECH have been reported in imaging literature. We present here a case of histopathologically diagnosed DIPNECH with diffusely increased In-octreotide uptake in both lungs.