MASH1 induces neuron transdifferentiation of adrenal medulla chromaffin cells / 中南大学学报(医学版)

OBJECTIVES@#Nerve growth factor (NGF) induces neuron transdifferentiation of adrenal medulla chromaffin cells (AMCCs) and consequently downregulates the secretion of epinephrine (EPI), which may be involved in the pathogenesis of bronchial asthma. Mammalian achaete scute-homologous 1 (MASH1), a key regulator of neurogenesis in the nervous system, has been proved to be elevated in AMCCs with neuron transdifferentiation in vivo. This study aims to explore the role of MASH1 in the process of neuron transdifferentiation of AMCCs and the mechanisms.@*METHODS@#Rat AMCCs were isolated and cultured. AMCCs were transfected with siMASH1 or MASH1 overexpression plasmid, then were stimulated with NGF and/or dexamethasone, PD98059 (a MAPK kinase-1 inhibitor) for 48 hours. Morphological changes were observed using light and electron microscope. Phenylethanolamine-N-methyltransferase (PNMT, the key enzyme for epinephrine synthesis) and tyrosine hydroxylase were detected by immunofluorescence. Western blotting was used to test the protein levels of PNMT, MASH1, peripherin (neuronal markers), extracellular regulated protein kinases (ERK), phosphorylated extracellular regulated protein kinases (pERK), and JMJD3. Real-time RT-PCR was applied to analyze the mRNA levels of MASH1 and JMJD3. EPI levels in the cellular supernatant were measured using ELISA.@*RESULTS@#Cells with both tyrosine hydroxylase and PNMT positive by immunofluorescence were proved to be AMCCs. Exposure to NGF, AMCCs exhibited neurite-like processes concomitant with increases in pERK/ERK, peripherin, and MASH1 levels (all P<0.05). Additionally, impairment of endocrine phenotype was proved by a signifcant decrease in the PNMT level and the secretion of EPI from AMCCs (all P<0.01). MASH1 interference reversed the effect of NGF, causing increases in the levels of PNMT and EPI, conversely reduced the peripherin level and cell processes (all P<0.01). MASH1 overexpression significantly increased the number of cell processes and peripherin level, while decreased the levels of PNMT and EPI (all P<0.01). Compared with the NGF group, the levels of MASH1, JMJD3 protein and mRNA in AMCCs in the NGF+PD98059 group were decreased (all P<0.05). After treatment with PD98059 and dexamethasone, the effect of NGF on promoting the transdifferentiation of AMCCs was inhibited, and the number of cell processes and EPI levels were decreased (both P<0.05). In addition, the activity of the pERK/MASH1 pathway activated by NGF was also inhibited.@*CONCLUSIONS@#MASH1 is the key factor in neuron transdifferentiation of AMCCs. NGF-induced neuron transdifferentiation is probably mediated via pERK/MASH1 signaling.

Feocromocitoma adrenal gigante derecho. Reporte de un caso / Right giant adrenal pheochromocytoma. A case report

Introducción. El feocromocitoma es una neoplasia endocrina productora de catecolaminas, poco común, que generalmente se origina en la medula suprarrenal, y rara vez en el tejido cromafín extraadrenal, dándosele el nombre de paraganglioma. Existe una gran variedad de signos y síntomas secundarios a la secreción excesiva de catecolaminas por lo que su diagnóstico y tratamiento oportunos son fundamentales para evitar complicaciones potencialmente fatales. Caso clínico. Paciente femenina de 54 años, con dolor abdominal intermitente y con aumento progresivo, localizado en el cuadrante superior derecho. Por estudios imagenológicos se diagnosticó una gran masa suprarrenal derecha, con pruebas de laboratorio que encontraron niveles de metanefrinas y catecolaminas en orina normales. Discusión. Debido al tamaño del tumor y al íntimo contacto con las estructuras adyacentes, se realizó la resección por vía abierta, sin complicaciones y con una buena evolución postoperatoria. El informe anatomopatológico confirmó el diagnóstico de feocromocitoma suprarrenal derecho. Conclusión. Aunque poco frecuente, el feocromocitoma es una patología que se debe sospechar ante la presencia de masas suprarrenales y alteraciones relacionadas con la secreción elevada de catecolaminas. Se debe practicar el tratamiento quirúrgico de forma oportuna.

Introduction. Pheochromocytoma is a rare catecholamine-producing endocrine neoplasm that generally originates in the adrenal medulla, and rarely in extra-adrenal chromaffin tissue, giving it the name of paraganglioma. There is a wide variety of signs and symptoms secondary to excessive secretion of catecholamines, so its timely diagnosis and treatment are essential to avoid potentially fatal complications. Clinical case. A 54-year-old female patient with intermittent abdominal pain and progressive increase, located in the right upper quadrant. By imaging studies, a large right adrenal mass was diagnosed, with laboratory tests that found normal levels of metanephrines and catecholamines in urine. Discussion. Due to the size of the tumor and the intimate contact with the adjacent structures, the resection was performed by open approach, without complications and with a good postoperative evolution. The pathology report confirmed the diagnosis of right adrenal pheochromocytoma. Conclusion. Although rare, pheochromocytoma is a pathology that should be suspected in the presence of adrenal masses and changes related to elevated catecholamine secretion. Surgical treatment should be performed in a timely manner.

Adrenalectomía laparoscópica / Laparoscopic adrenalectomy

Introducción: desde el año 1997 se comenzó a realizar la adrenalectomía laparoscópica en nuestro centro. Objetivo: analizar los resultados de la adrenalectomía laparoscópica desde su implementación en el servicio de cirugía general del Hospital Clínico Quirúrgico Hermanos Ameijeiras. Métodos: Se realizó un estudio descriptivo de los resultados obtenidos en 160 pacientes a los que se les realizó adrenalectomía por vía laparoscópica, en el período comprendido desde noviembre de 1997 hasta septiembre del año 2017 en el servicio de cirugía general del Hospital Clínico Quirúrgico Universitario Hermanos Ameijeiras. Se empleó la técnica laparoscópica con abordaje lateral intraperitoneal en la mayoría de los casos y el abordaje en decúbito supino en 2 casos para la adrenalectomía bilateral. Resultados: se realizaron 162 adrenalectomías laparoscópicas en 160 pacientes, ya que a dos pacientes se les realizó la adrenalectomía bilateral en un tiempo. La edad promedio fue de 44,8 años. La indicación quirúrgica fue el incidentaloma en 68 pacientes (42,5 pr ciento), el síndrome de Cushing en 27 (16,8 por ciento), feocromocitoma en 26 (16,25 por ciento), la Enfermedad de Cushing con fracaso del tratamiento neuroquirúrgico en 12 (7,5 por ciento), mielolipomas en 7 (4,37 por ciento), tumor adrenal en 6 (3,75 por ciento), tumor metastásico en 5 (3,1 por ciento), quistes adrenales en 4 (2,5 por ciento), hiperaldosteronismo primario en 3 (1,87 por ciento), tumor virilizante adrenal en 1 paciente y 1 paciente con un Síndrome de secreción ectópica de ACTH que le provocaba un Síndrome de Cushing complicado. Predominaron las lesiones del lado izquierdo en 86 pacientes, 72 del lado derecho y 2 bilaterales. Fueron convertidos a cirugía convencional 2 pacientes (1,25 por ciento). El tiempo quirúrgico promedio fue de 82 minutos. La estadía posoperatoria promedio fue de 2.5 días. Conclusiones: la adrenalectomía laparoscópica es una técnica reproducible y segura con las ventajas inherentes a la cirugía laparoscópica(AU)

Introduction: As far as 1997, the performing of laparoscopic adrenalectomy started in our center. Objective: To analyze the results of laparoscopic adrenalectomy since its implementation in the general surgery service of Hermanos Ameijeiras Clinical Surgical Hospital. Methods: A descriptive study was carried out with the results obtained from 160 patients who underwent laparoscopic adrenalectomy, in the period from November 1997 to September 2017, in the general surgery service of Hermanos Ameijeiras University Clinical Surgical Hospital. The laparoscopic technique with intraperitoneal lateral approach was used in the majority of cases and the supine approach was used in two cases for bilateral adrenalectomy. Results: 162 laparoscopic adrenalectomies were performed in 160 patients, since two patients underwent bilateral adrenalectomy at one time. The average age was 44.8 years. Surgical indication cases were incidentalomas, in 68 patients (42.5 percent), Cushing's syndrome in 27 (16.8 percent), pheochromocytomas in 26 (16.25 percent), Cushing's disease with neurosurgical treatment failure in 12 (7.5 percent), myelolipomas in 7 (4.37 percent), adrenal tumor in 6 (3.75 percent), metastatic tumor in 5 (3.1 percent), adrenal cysts in 4 (2.5 percent), primary hyperaldosteronism in 3 (1.87 percent), adrenal virilizing tumor in 1 patient, and 1 patient with an ectopic ACTH secretion syndrome that caused a complicated Cushing's syndrome. Lesions on the left side were predominant in 86 patients, 72 on the right side and two bilateral. Two patients (1.25 percent) were converted to conventional surgery. The average surgical time was 82 minutes. The average postoperative stay was 2.5 days. Conclusions: Laparoscopic adrenalectomy is a reproducible and safe technique with the advantages inherent to laparoscopic surgery(AU)

Caso clínico: Feocromocitoma Gigante / Case Report: Giant Pheocromocytoma

INTRODUCCIÓN: El feocromocitoma es una neoplasia neuroendocrina localizada en la médula adrenal, llamado paraganglioma cuando su ubicación es extraadrenal. Su incidencia anual es de 2-8 por millón de personas, sin predilección de sexo. Su cuadro clínico se caracteriza por: cefalea, diaforesis, taquicardia e hipertensión arterial. El tratamiento es la resección quirúrgica con una preparación preoperatoria multidisciplinaria. CASO CLÍNICO: Se trata de una paciente de 36 años, femenina con antecedentes de hipertensión arterial de un año de evolución, acompañado de cefalea, pérdida de peso, dolor abdominal, diaforesis, malestar general y otros; hospitalizada por varias ocasiones debido a crisis hipertensivas. Tensión arterial 180/120 mmHg, Frecuencia cardíaca 90/min, Índice de masa corporal 19.2 Kg/m2. Abdomen: masa palpable en hipocondrio y flaco izquierdos de aproximadamente 10 cm, no doloroso a la palpación. EVOLUCIÓN: Dentro de los exámenes complementarios, la determinación de catecolaminas en plasma fueron normales, en la tomografía computarizada se evidenció una masa retroperitoneal que involucraba riñón y suprarrenal izquierdos; ante la persistencia de hipertensión, se realiza la resección de la neoplasia por laparotomía más nefrectomía izquierda, flebotomía de cava inferior y transversectomía. Como complicación en el postoperatorio inmediato presentó hemoperitoneo requiriendo relaparotomía con esplenectomía, además adquirió neumonía la cual fue superada satisfactoriamente y fue dada el alta médica en buenas condiciones. CONCLUSIONES: El feocromocitoma es una patología infrecuente y compleja, cuya resolución quirúrgica es mandatoria, con una preparación prequirúrgica multidisciplinaria para disminuir al máximo la morbimortalidad y con un seguimiento a largo plazo en todos los casos.(AU)

INTRODUCTION: Pheochromocytoma is a neuroendocrine tumor located in the adrenal medulla or paraganglioma when its location is extraadrenal. The annual incidence is 2-8million people, no sex predilection. Clinical symptoms are characterised by: headache, diaphoresis,tachycardia, and hypertension. The treatment is surgical resection with a multidisciplinary preoperative preparation. CASE REPORT: This isa36 year old female patient,withahistory of hypertension forayear,accompanied by headache, weight loss, abdominal pain, diaphoresis, malaise and others; hospitalized for several times due to hypertensive crises. BP: 180/120 mmHg; HR: 90 per minute; BMI 19.2 kg / m2. Abdomen: palpablemass in upper quadrant and left flank of approximately 10 cm, not painful on palpation. EVOLUTION: About the examinations, the plasma catecholamines tests were normal and the CT scan showed a retroperitoneal mass which involved kidney and adrenal on left side. At the persistence of hypertension, the resection of the tumor was performed by laparotomy; also was performed left nephrectomy, phlebotomy of inferior cava and the resection ofthe transverse colon. Inthe immediatepostoperativeperiod,thepatientpresentedhemoperitoneumandasplenectomy was performed; also contracted pneumonia which was successfully treated. She left the hospital in good condition. CONCLUSIONS: The Pheochromocytoma is an infrequent and complex disease, whose surgical treatment is mandatory. A multidisciplinary preoperative preparation is important to reduce the morbidity andmortality associated and the follow-upmust be long termin all cases.(AU)

Feocromocitoma quístico gigante: reporte de un caso / Pheochromocytoma giant cystic: a case report

El feocromocitoma quístico gigante es tumor adrenal raro en el que predomina el curso asintomático; por lo que muchos de los casos no son diagnosticados hasta el momento de la cirugía. La simple movilización del tumor se asocia con el paso a la sangre de grandes cantidades de catecolaminas y a una elevada morbimortalidad.; por esta razón la cirugía per se y su manejo perioperatorio constituyen un enorme desafío. En este artículo se presenta el caso de un feocromocitoma gigante maligno (35 cm) que ocupaba todo el hemiabdomen derecho. Aun con el diagnóstico preoperatorio de feocromocitoma, el bloqueo farmacológico preoperatorio y las medidas intraoperatorias, el paciente falleció poco antes de que finalizara la cirugía.

The giant cystic pheochromocytoma is a rare adrenal tumor in the predominantly asymptomatic course; so many cases are not diagnosed until the time of surgery. The simple mobilization of the tumor is associated with the passage to the blood of large amounts of catecholamines and high morbidity and mortality. So the surgery itself and perioperative management are a huge challenge. This article describes the case of a malignant giant pheochromocytoma (35 cm) which occupied the entire right abdomen. Even with the preoperative diagnosis of pheochromocytoma, pharmacological blockade preoperative and intraoperative measures, the patient died shortly before the end of surgery.

Dual control of the vestibulosympathetic reflex following hypotension in rats

Orthostatic hypotension (OH) is associated with symptoms including headache, dizziness, and syncope. The incidence of OH increases with age. Attenuation of the vestibulosympathetic reflex (VSR) is also associated with an increased incidence of OH. In order to understand the pathophysiology of OH, we investigated the physiological characteristics of the VSR in the disorder. We applied sodium nitroprusside (SNP) to conscious rats with sinoaortic denervation in order to induce hypotension. Expression of pERK in the intermediolateral cell column (IMC) of the T4~7 thoracic spinal regions, blood epinephrine levels, and blood pressure were evaluated following the administration of glutamate and/or SNP. SNP-induced hypotension led to increased pERK expression in the medial vestibular nucleus (MVN), rostral ventrolateral medullary nucleus (RVLM) and the IMC, as well as increased blood epinephrine levels. We co-administered either a glutamate receptor agonist or a glutamate receptor antagonist to the MVN or the RVLM. The administration of the glutamate receptor agonists, AMPA or NMDA, to the MVN or RVLM led to elevated blood pressure, increased pERK expression in the IMC, and increased blood epinephrine levels. Administration of the glutamate receptor antagonists, CNQX or MK801, to the MVN or RVLM attenuated the increased pERK expression and blood epinephrine levels caused by SNP-induced hypotension. These results suggest that two components of the pathway which maintains blood pressure are involved in the VSR induced by SNP. These are the neurogenic control of blood pressure via the RVLM and the humoral control of blood pressure via epinephrine release from the adrenal medulla.

Corrigendum to: Gintonin facilitates catecholamine secretion from the perfused adrenal medulla

The original version of this article contained misspelled name of authors. The name of Seung-Yeol Na is replaced with Seung-Yeol Nah. The name of Mi-Sung Choi is replaced with Mee-Sung Choi.

Renal intercalated cells and blood pressure regulation

Type B and non-A, non-B intercalated cells are found within the connecting tubule and the cortical collecting duct. Of these cell types, type B intercalated cells are known to mediate Cl⁻ absorption and HCO₃⁻ secretion largely through pendrin-dependent Cl⁻/HCO₃⁻ exchange. This exchange is stimulated by angiotensin II administration and is also stimulated in models of metabolic alkalosis, for instance after aldosterone or NaHCO₃ administration. In some rodent models, pendrin-mediated HCO₃⁻ secretion modulates acid-base balance. However, the role of pendrin in blood pressure regulation is likely of more physiological or clinical significance. Pendrin regulates blood pressure not only by mediating aldosterone-sensitive Cl⁻ absorption, but also by modulating the aldosterone response for epithelial Na⁺ channel (ENaC)-mediated Na⁺ absorption. Pendrin regulates ENaC through changes in open channel of probability, channel surface density, and channels subunit total protein abundance. Thus, aldosterone stimulates ENaC activity through both direct and indirect effects, the latter occurring through its stimulation of pendrin expression and function. Therefore, pendrin contributes to the aldosterone pressor response. Pendrin may also modulate blood pressure in part through its action in the adrenal medulla, where it modulates the release of catecholamines, or through an indirect effect on vascular contractile force. This review describes how aldosterone and angiotensin II-induced signaling regulate pendrin and the contributory role of pendrin in distal nephron function and blood pressure.

Renal intercalated cells and blood pressure regulation

Type B and non-A, non-B intercalated cells are found within the connecting tubule and the cortical collecting duct. Of these cell types, type B intercalated cells are known to mediate Cl⁻ absorption and HCO₃⁻ secretion largely through pendrin-dependent Cl⁻/HCO₃⁻ exchange. This exchange is stimulated by angiotensin II administration and is also stimulated in models of metabolic alkalosis, for instance after aldosterone or NaHCO₃ administration. In some rodent models, pendrin-mediated HCO₃⁻ secretion modulates acid-base balance. However, the role of pendrin in blood pressure regulation is likely of more physiological or clinical significance. Pendrin regulates blood pressure not only by mediating aldosterone-sensitive Cl⁻ absorption, but also by modulating the aldosterone response for epithelial Na⁺ channel (ENaC)-mediated Na⁺ absorption. Pendrin regulates ENaC through changes in open channel of probability, channel surface density, and channels subunit total protein abundance. Thus, aldosterone stimulates ENaC activity through both direct and indirect effects, the latter occurring through its stimulation of pendrin expression and function. Therefore, pendrin contributes to the aldosterone pressor response. Pendrin may also modulate blood pressure in part through its action in the adrenal medulla, where it modulates the release of catecholamines, or through an indirect effect on vascular contractile force. This review describes how aldosterone and angiotensin II-induced signaling regulate pendrin and the contributory role of pendrin in distal nephron function and blood pressure.

Gintonin facilitates catecholamine secretion from the perfused adrenal medulla

The present study was designed to investigate the characteristics of gintonin, one of components isolated from Korean Ginseng on secretion of catecholamines (CA) from the isolated perfused model of rat adrenal gland and to clarify its mechanism of action. Gintonin (1 to 30 µg/ml), perfused into an adrenal vein, markedly increased the CA secretion from the perfused rat adrenal medulla in a dose-dependent fashion. The gintonin-evoked CA secretion was greatly inhibited in the presence of chlorisondamine (1 µM, an autonomic ganglionic bloker), pirenzepine (2 µM, a muscarinic M₁ receptor antagonist), Ki14625 (10 µM, an LPA₁/₃ receptor antagonist), amiloride (1 mM, an inhibitor of Na⁺/Ca²⁺ exchanger), a nicardipine (1 µM, a voltage-dependent Ca²⁺ channel blocker), TMB-8 (1 µM, an intracellular Ca²⁺ antagonist), and perfusion of Ca²⁺-free Krebs solution with 5mM EGTA (a Ca²⁺chelater), while was not affected by sodium nitroprusside (100 µM, a nitrosovasodialtor). Interestingly, LPA (0.3~3 µM, an LPA receptor agonist) also dose-dependently enhanced the CA secretion from the adrenal medulla, but this facilitatory effect of LPA was greatly inhibited in the presence of Ki 14625 (10 µM). Moreover, acetylcholine (AC)-evoked CA secretion was greatly potentiated during the perfusion of gintonin (3 µg/ml). Taken together, these results demonstrate the first evidence that gintonin increases the CA secretion from the perfused rat adrenal medulla in a dose-dependent fashion. This facilitatory effect of gintonin seems to be associated with activation of LPA- and cholinergic-receptors, which are relevant to the cytoplasmic Ca²⁺ increase by stimulation of the Ca²⁺ influx as well as by the inhibition of Ca²⁺ uptake into the cytoplasmic Ca²⁺ stores, without the increased nitric oxide (NO). Based on these results, it is thought that gintonin, one of ginseng components, can elevate the CA secretion from adrenal medulla by regulating the Ca²⁺ mobilization for exocytosis, suggesting facilitation of cardiovascular system. Also, these findings show that gintonin might be at least one of ginseng-induced hypertensive components.

Effects of electroacupuncture on anxiety and sympathetic-adrenal medulla system in rats with insomnia / 中国针灸

<p><b>OBJECTIVE</b>To explore the action mechanism of electroacupuncture (EA) at "Shenmen" (HT 7) and "Sanyinjiao" (SP 6) on insomnia.</p><p><b>METHODS</b>Thirty SD rats were randomly divided into a blank group, a model group and an EA group, 10 cases in each group. The insomnia model was made by immobilization method in the model group and EA group. After model establishment, rats in the blank group and model group were treated with fixation and no treatment was given. Rats in the EA group were treated with EA at "Shenmen" (HT 7) and "San-yinjiao" (SP 6) for 15 min, once a day for 4 days. After treatment, the level of daytime and nighttime activity, open-arm entry percentage and open-arm time percentage of elevated plus-maze test were measured; the content of noradrenaline (NE), dopamine (DA) and epinephrine (EPI) in plasma and NE, DA in thalamus and brainstem were detected by using euzymelinked immunosorbent assay method.</p><p><b>RESULTS</b>Compared with the blank group, the daytime activity was increased and nighttime activity was reduced in the model group (both P<0. 05); the open-arm entry percentage and open-arm time percentage of elevated plus-maze test were both reduced in the model group (both P<0. 05); the contents of NE, DA, EPI in the plasma and NE, DA in thalamus and brainstem were increased in the model group (all P<0. 05). Compared with the model group, the daytime activity was reduced and nighttime activity was increased in the EA group (both P<0. 05); the open-arm entry percentage and open-arm time percentage of elevated plus-maze test were both increased in the EA group (both P<0. 05); the contents of NE, DA, EPI in the plasma and NE, DA in thalamus and brainstem were reduced in the EA group (all P< 0. 05).</p><p><b>CONCLUSION</b>Electroacupuncture at "Shenmen" (HT 7) and "Sanyinjiao" (SP 6) can restrain the over-activity of the sympathetic-adrenal medullary system to treat the insomnia.</p>

Pathways of Neurogenic and Humoral Control in the Vestibulosympathetic Reflex of Conscious Rats / 대한평형의학회지

OBJECTIVE: The vestibular system contributes control of blood pressure during postural changes through the vestibulosympathetic reflex. In the vestibulosympathetic reflex, afferent signals from the peripheral vestibular receptors are transmitted to the vestibular nuclei, rostral ventrolateral medullary nuclei, and then to the intermediolateral cell column of the thoracolumbar spinal cord. Physiological characteristics of the vestibulosympathetic reflex in terms of neurogenic and humoral control of blood pressure were investigated in this study. METHODS: Conscious rats with sinoaortic denervation were used for removal of baroreceptors in reflex control of blood pressure, and hypotension was induced by intravenous infusion of sodium nitroprusside (SNP). Expression of c-Fos protein was measured in the medial vestibular nuclei (MVN), rostral vestrolateral medullary nuclei(RVLM), and intermediolateral cell column (IMC) in T4-7, and levels of blood epinephrine were measured following SNP-induced hypotension. RESULTS: SNP-induced hypotension significantly increased expression of c-Fos protein in the MVN, RVLM, and IMC, also significantly increased level of blood epinephrine compared to normotensive control animals. CONCLUSION: These results suggest that the vestibulosympathetic reflex regulates blood pressure through neurogenic control including MVN, RVLM, and IMC, also through humoral control including epinephrine secretion by the adrenal medulla following SNP-induced hypotension. The physiological characteristics of the reflex may contribute to basic treatment of impairment of blood pressure control during postural changes.

A Case of Pheochromocytoma Initially Manifesting as Acute Myocardial Infarction

Pheochromocytomas are rare catecholamine-secreting neuroendocrine tumors arising from chromaffin cells in the adrenal medulla. Typical classic triad are consisted of headaches, palpitations, and profuse diaphoresis. But some patients with pheochromocytomas have other cardiovascular manifestations such as left ventricular hypertrophy, congestive heart failure, and cardiac arrhythmia. Rarely, pheochromocytomas manifest as acute myocardial infarction leading to delayed diagnosis and treatment. We experienced one case of pheochromocytoma initially manifesting as acute myocardial infarction which showed normal coronary artery on coronary angiography. Pheochromocytoma should be suspected and evaluated in patients with acute myocardial infarction whose coronary angiography shows normal coronary without definite thrombosis.

Inhibitory Effects of Ginsenoside-Rb2 on Nicotinic Stimulation-Evoked Catecholamine Secretion

The aim of the present study was to investigate whether ginsenoside-Rb2 (Rb2) can affect the secretion of catecholamines (CA) in the perfused model of the rat adrenal medulla. Rb2 (3~30 microM), perfused into an adrenal vein for 90 min, inhibited ACh (5.32 mM)-evoked CA secretory response in a dose- and time-dependent fashion. Rb2 (10 microM) also time-dependently inhibited the CA secretion evoked by DMPP (100 microM, a selective neuronal nicotinic receptor agonist) and high K+ (56 mM, a direct membrane depolarizer). Rb2 itself did not affect basal CA secretion (data not shown). Also, in the presence of Rb2 (50 microg/mL), the secretory responses of CA evoked by veratridine (a selective Na+ channel activator (50 microM), Bay-K-8644 (an L-type dihydropyridine Ca2+ channel activator, 10 microM), and cyclopiazonic acid (a cytoplasmic Ca2+-ATPase inhibitor, 10 microM) were significantly reduced, respectively. Interestingly, in the simultaneous presence of Rb2 (10 microM) and L-NAME (an inhibitor of NO synthase, 30 microM), the inhibitory responses of Rb2 on ACh-evoked CA secretory response was considerably recovered to the extent of the corresponding control secretion compared with the inhibitory effect of Rb2-treatment alone. Practically, the level of NO released from adrenal medulla after the treatment of Rb2 (10 microM) was greatly elevated compared to the corresponding basal released level. Collectively, these results demonstrate that Rb2 inhibits the CA secretory responses evoked by nicotinic stimulation as well as by direct membrane-depolarization from the isolated perfused rat adrenal medulla. It seems that this inhibitory effect of Rb2 is mediated by inhibiting both the influx of Ca2+ and Na+ into the adrenomedullary chromaffin cells and also by suppressing the release of Ca2+ from the cytoplasmic calcium store, at least partly through the increased NO production due to the activation of nitric oxide synthase, which is relevant to neuronal nicotinic receptor blockade.

Comparison of Inhibitory Effects between Enalapril and Losartan on Adrenal Catecholamine Secretion

BACKGROUND: The present study was attempted to compare enalapril, an angiotensin-converting enzyme inhibitor with losartan an angiotensin II (Ang II) receptor blocker in the inhibitory effects on the secretion of catecholamines (CA) from the perfused model of the rat adrenal gland. METHODS: The adrenal gland was isolated and perfused with Krebs-bicarbonate. CA was measured directly by using the fluorospectrophotometer. RESULTS: Both enalapril and losartan during perfusion into an adrenal vein for 90 minutes inhibited the CA release evoked by acetylcholine (ACh), 1.1-dimethyl-4-phenyl piperazinium (DMPP, a selective Nn agonist), high K+ (a direct membrane-depolarizer), 3-(m-chloro-phenyl-carbamoyl-oxy-2-butynyl-trimethyl ammonium (McN-A-343, a selective M1 agonist), and Ang II in a time-dependent manner. Also, in the presence of enalapril or losartan, the CA release evoked by veratridine (an activator of voltage-dependent Na+ channels), 6-dimethyl-3-nitro-4-(2-trifluoromethyl-phenyl)-pyridine-5-carboxylate (BAY-K-8644, an L-type Ca2+ channel activator), and cyclopiazonic acid (a cytoplasmic Ca2+-ATPase inhibitor) were significantly reduced. Based on the same concentration of enalapril and losartan, for the CA release evoked by ACh, high K+, DMPP, McN-A-343, Ang II, veratridine, BAY-K-8644, and cyclopiazonic acid, the following rank order of inhibitory potency was obtained: losartan > enalapril. In the simultaneous presence of enalapril and losartan, ACh-evoked CA secretion was more strongly inhibited compared with that of enalapril- or losartan-treated alone. CONCLUSIONS: Collectively, these results demonstrate that both enalapril and losartan inhibit the CA secretion evoked by activation of both cholinergic and Ang II type-1 receptors stimulation in the perfused rat adrenal medulla. When these two drugs were used in combination, their effects were enhanced, which may also be of clinical benefit. Based on concentration used in this study, the inhibitory effect of losartan on the CA secretion seems to be more potent than that of enalapril.

Paraganglioma metastásico: imagen con 18F-fluordesoxiglucosa-tomografía por emisión de positrones / Metastatic paraganglioma: image with F18-FDG- PET/CT

Los paragangliomas son tumores neuroendocrinos poco frecuentes que pueden originarse en cualquier lugar a lo largo del sistema paraganglial. La mayoría son benignos y de progresión lenta, sin embargo un 10% aproximadamente presentan metástasis. El 80-85% de estos tumores surgen de la médula suprarrenal y se nombran feocromocitomas, mientras que el 15-20% se encuentran en tejidos cromafines a nivel extra-adrenal y se conocen como paragangliomas. Tienen variantes hereditarias (25%), también pueden manifestarse con multifocalidad. Pueden aparecer en cualquier parte del sistema paraganglial y estar asociados con el tejido nervioso simpático (médula adrenal, el órgano de Zuckerkandl, u otras células cromafines que puedan persistir más allá de la embriogénesis), o con el sistema nervioso parasimpático (quimiorreceptores, que se encuentra principalmente en cabeza y cuello). Por lo tanto, los paragangliomas pueden estar distribuidos desde la base del cráneo hasta el sacro. Las imágenes de medicina nuclear ayudan a delinear plenamente la enfermedad.

The paragangliomas are a rare neuroendocrine group of tumors that can occur anywhere along paraganglia system. Most of them are benign and of slow progression, however about 10% of them will have metastases. The large majority (80-85%) of these tumors arise from the adrenal medulla and are called pheochromocytomas, while 15-20% originate in chromaffin tissue at extra-adrenal sites, and are called paragangliomas. There are inherited variants (25%), and the disease may also present with multifocality. They can appear anywhere in paraganglia system and may be associated with sympathetic nervous tissue (adrenal medulla, the organ of Zuckerkandl, or other chromaffin cells that can persist beyond embryogenesis), or the parasympathetic nervous system (chemoreceptors, which are found mainly in the head and neck). Therefore, paragangliomas can be distributed from the base of the skull to the sacrum. Nuclear medicine imaging can help to fully define the disease. © 2013 Instituto Nacional de Cancerología. Published by Elsevier España, S.L. All rights reserved.

Extra Adrenal Pheochromocytoma Presenting as Hypertensive Crisis in a Young Male.

Pheochromocytoma is a tumor of aderenal medulla which secrets catecholamines and usually presents as hypertension. Extra-adrenal pheochromocytomas are extremely rare. They occur in the organ of zukerkundle, bladder, retroperitonium, posterior mediastinum and sympathetic chain. We present a case of a young male who presented with hypertension and eventually was found to have extra adrenal pheochromocytoma of the bladder.

Feocromocitoma asintomático / Asymptomatic pheochromocytoma

El feocromocitoma es un tumor que produce catecolaminas,mayor responsable de la hipertensión arterial en jóvenes,con mayor frecuencia se localiza en la medula suprarrenal, unilateral.Generalmente asociado con neoplasia endócrina múltiple.Los pacientes presentan una serie de síntomas, entre ellosla hipertensión arterial.Se presenta el caso de una paciente de 31 años, con doloren hipocondrio derecho de un año de evolución, tipo pesadezy pérdida de peso de 3 kg. Al examen físico se constató tumoraciónen hipocondrio derecho que llega a epigastrio, de 12cm de diámetro. Con el diagnóstico de tumor retroperitonealobtenido por imágenes se decide una laparotomía exploradoradonde se visualizó un tumor de 18cm. de diámetro, sólido, enpolo superior del riñón derecho, adherido a vena cava. Se realizóuna exéresis tumoral y el informe de anatomía patológicaconfirmó feocromocitoma

A Case of Pheochromocytoma Associated with Diabetic Ketoacidosis and Infective Endocarditis / 임상당뇨병

Pheochromocytoma is a rare neuroendocrine tumor that is usually derived from adrenal medulla or chromaffin cells along with sympathetic ganglia. In Western countries, the prevalence of pheochromocytoma is estimated to be between 1:6,500 and 1:2,500, compared with an incidence in the United States of 500 to 1,100 cases per year. Despite this low incidence, pheochromocytoma should always be considered for differential diagnoses because previous studies have shown that this condition can be cured in approximately 90% of cases. However, an untreated tumor is likely to be fatal due to catecholamine-induced malignant hypertension, heart failure, myocardial infarction, stroke, ventricular arrhythmias or metastatic disease. Symptoms that result primarily from excess circulating catecholamines and hypertension include severe headaches, generalized inappropriate sweating and palpitations (with tachycardia or occasionally bradycardia). Pheochromocytoma, however, has highly variable and heterogeneous clinical manifestations, including fever, general weakness and dyspepsia, and can be observed in patients who are suffering from infectious diseases. Several of such case reports have been presented, but most of these included infectious patients with high blood pressure and severe fluctuations. In this study, we presented the case of a 53-year-old male who showed normal blood pressure, but had a sustained fever. He was diagnosed with diabetic ketoacidosis, infective endocarditis and asymptomatic adrenal incidentaloma. Despite treatment with antibiotics and valve replacement, the fever persisted. After the patient underwent evaluation for the fever, adrenal incidentaloma was identified as pheochromocytoma. After removal of the abdominal mass, his fever improved.

Influence of Fimasartan (a Novel AT1 Receptor Blocker) on Catecholamine Release in the Adrenal Medulla of Spontaneously Hypertensive Rats

The aim of this study was to determine whether fimasartan, a newly developed AT1 receptor blocker, can affect the CA release in the isolated perfused model of the adrenal medulla of spontaneously hypertensive rats (SHRs). Fimasartan (5~50 microM) perfused into an adrenal vein for 90 min produced dose- and time-dependently inhibited the CA secretory responses evoked by ACh (5.32 mM), high K+ (56 mM, a direct membrane depolarizer), DMPP (100 microM) and McN-A-343 (100 microM). Fimasartan failed to affect basal CA output. Furthermore, in adrenal glands loaded with fimasartan (15 microM), the CA secretory responses evoked by Bay-K-8644 (10 microM, an activator of L-type Ca2+ channels), cyclopiazonic acid (10 microM, an inhibitor of cytoplasmic Ca(2+)-ATPase), and veratridine (100 microM, an activator of Na+ channels) as well as by angiotensin II (Ang II, 100 nM), were markedly inhibited. In simultaneous presence of fimasartan (15 microM) and L-NAME (30 microM, an inhibitor of NO synthase), the CA secretory responses evoked by ACh, high K+, DMPP, Ang II, Bay-K-8644, and veratridine was not affected in comparison of data obtained from treatment with fimasartan (15 microM) alone. Also there was no difference in NO release between before and after treatment with fimasartan (15 microM). Collectively, these experimental results suggest that fimasartan inhibits the CA secretion evoked by Ang II, and cholinergic stimulation (both nicotininc and muscarinic receptors) as well as by membrane depolarization from the rat adrenal medulla. It seems that this inhibitory effect of fimasartan may be mediated by blocking the influx of both Na+ and Ca2+ through their ion channels into the rat adrenomedullary chromaffin cells as well as by inhibiting the Ca2+ release from the cytoplasmic calcium store, which is relevant to AT1 receptor blockade without NO release.