Anti-cancer potential of MAPK pathway inhibition in paragangliomas-effect of different statins on mouse pheochromocytoma cells

NARCIS (Netherlands)

Fliedner, S.M.; Engel, T.G.P.; Lendvai, N.K.; Shankavaram, U.; Nolting, S.; Wesley, R.; Elkahloun, A.G.; Ungefroren, H.; Oldoerp, A.; Lampert, G.; Lehnert, H.; Timmers, H.J.; Pacak, K.

2014-01-01

To date, malignant pheochromocytomas and paragangliomas (PHEOs/PGLs) cannot be effectively cured and thus novel treatment strategies are urgently needed. Lovastatin has been shown to effectively induce apoptosis in mouse PHEO cells (MPC) and the more aggressive mouse tumor tissue-derived cells

Catecholamine induced cardiomyopathy in pheochromocytoma

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Ron Thomas Varghese

2013-01-01

Full Text Available Catecholamine induced cardiomyopathy in the setting of pheochromocytoma is an unusual clinical entity. Earlier studies have reported left ventricular dysfunction in around 10% of subjects with pheochromocytoma. [1] Catecholamine induced vasoconstriction, direct toxic effect of byproducts of catecholamine degradation and direct receptor-mediated mechanisms are thought to contribute to cardiomyopathy in subjects with pheochromocytoma. The presentation remains a diagnostic challenge as patients may already have hypertensive heart disease and acute coronary syndrome on account of uncontrolled secondary hypertension. We report a case of a 42-year-old male, who presented with features of pheochromocytoma induced cardiomyopathy.

The Epidemiology of Pheochromocytoma

DEFF Research Database (Denmark)

Ebbehoj, A; Søndergaard, Esben; Trolle, Christian

Pheochromocytoma is a rare disease but frequently poses a diagnostic dilemma due to the unspecific symptoms and its potentially life-threatening nature. There is a perception of an increase in the incidence of pheochromocytomas in recent years, but no data on time trends exist. We obtained data f...

Primary meningeal pheochromocytoma: a case report

Energy Technology Data Exchange (ETDEWEB)

Yoon, Il Ju; Suh, Hyoung Sim [Myung-Ji St. Mary' s Hospital, Seoul (Korea, Republic of); Kim, Sung Nam [Green Cross Reference Lab, Seoul (Korea, Republic of)

2007-04-15

Pheochromocytoma is a rare endocrine tumor arising from the chromaffin tissue, and it is able to produce and secrete catecholamines. Lymph nodes, liver, lung and bone are the most frequent sites of metastasis. We report here on a case of pheochromocytoma arising from the dura in a patient who was surgically treated for bilateral pheochromocytoma five years previously.

Pheochromocytoma

Science.gov (United States)

... foods include: Some cheeses Some beers and wines Chocolate Dried or smoked meats Certain medications that can ... blood pressure with current treatment plan A family history of pheochromocytoma A family history of a related ...

The HSP90 inhibitor 17-AAG exhibits potent antitumor activity for pheochromocytoma in a xenograft model.

Science.gov (United States)

Xu, Yunze; Zhu, Qi; Chen, Dongning; Shen, Zhoujun; Wang, Weiqing; Ning, Guang; Zhu, Yu

2015-07-01

This study aims to investigate the effect of heat shock protein 90 (HSP90) inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) in the malignant pheochromocytoma using a xenograft mouse model. Treatment with 17-AAG induced a marked reduction in the volume and weight of PC12 pheochromocytoma cell tumor xenografts in mice. Furthermore, 17-AAG also significantly inhibited the expression of HSP90 and its client proteins. Our results validated HSP90 as an important target in pheochromocytoma and provided rationale for the testing of HSP90 inhibitors as a promising therapeutic agent in the antitumor therapy of pheochromocytoma.

Pheochromocytomas / Paragangliomas and two cases

African Journals Online (AJOL)

micturition, and various drugs (gluca- gon, tyramine, tricylic antidepressants, etc). Paroxysms usually last minutes to an hour. Note. Many of the symptoms and signs associated with pheochromocytoma are fairly typical of many other clinical con- ditions (table 1). Pheochromocytoma is therefore often referred to as “the great.

Simultaneous adrenal pheochromocytoma and carotid body paraganglioma in a woman

Energy Technology Data Exchange (ETDEWEB)

Han, Eun Ji; Lee, Sang Hoon; Song, In Uk; Chung, Yong An; Maeng, Lee So [The Catholic Univ. of Korea, Incheon (Korea, Republic of)

2012-03-15

Simultaneous occurrence of carotid body tumor and pheochromocytoma is rare. Most pheochromocytomas have grown on adrenal medulla, but some of the pheochromocytoma patients have multifocal paragangliomas arising from extraaderenal tissues. Pheochromocytomas and paragangliomas occur as sporadic tumors or they can be associated with several hereditary syndromes such as (1) multiple endocrine neoplasia type 2 (MEN 2), (2) Von Hippel Lindau disease (VHL) and (3) neurofibromatosis type 1 as an unusual genetic cause of pheochromocytomas. Genetic testing is recommended for patients with an apparently sporadic pheochromocytoma under the age of 20 years with a family history or features suggestive of hereditary pheochromocytoma or for patients with sympathetic paragangliomas. For individuals who do not meet these criteria, genetic testing is optional. Discovery of pheochromocytoma or paraganglioma in a patient should lead to a careful search to rule out multifocal lesions and/or hereditary syndromes. The diagnosis of pheochromocytoma and paraganglioma is made by biochemical testing, and imaging is done to localize the tumor for surgical planning. F 18 FDG PET has proved to be an effective tool in the localization of pheochromocytomas and paragangliomas.

The Epidemiology of Pheochromocytoma - Is the Incidence Increasing?

DEFF Research Database (Denmark)

Ebbehoj, A; Søndergaard, Esben; Trolle, Christian

with pheochromocytoma, but the true incidence, morbidity and mortality associated with pheochromocytoma remains to be fully elucidated. Materials and methods The cohort of potential cases of pheochromocytoma patients was identified with a data extract on relevant diagnoses from the National Patient Registry covering...

Feocromocitoma em criança Pheochromocytoma in childhood

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Gesmar Volga Haddad Herdy

2005-03-01

Full Text Available Feocromocitoma é uma neoplasia de células cromafins que causa sintomas e sinais decorrentes da libertação de catecolminas e é muito rara em crianças. Relatamos um caso feocromocitoma em criança, com difícil manejo clínico, confirmado também pela anatomia-patológica e curado após a ressecção cirúrgica.Pheochromocytoma is a neoplasia of chromaffin cells that is very rare in children. Its signs and symptoms result from the release of catecholamines. We report the case of a child with pheochromocytoma of difficult clinical management, confirmed on the anatomicopathological study, and cured after surgical resection.

[Malignant pheochromocytoma].

Science.gov (United States)

Mornex, R; Berthezene, F; Peyrin, L; Tran Minh, V; Martin, J P; Fulchiron, D

1979-11-01

The reported incidence of malignant pheochromocytoma varies from series to series. In this series 4 cases (7.2 p. 100) were observed out of a total of 55. In two cases the tumour progressed rapidly but in the other two cases, metastases were detected 3 to 12 years after the apparent cure of a histologically benign pheochromocytoma. The urinary levels of catecholamines and their metabolites gave no indication of the underlying malignancy. The diagnosis was only made from the clinical and radiological detection of metastases (2 hepatic, 2 bone). There is no satisfactory treatment and various therapeutic methods have to be used in succession; surgery for a single metastasis, radiotherapy and antiadrenergic agents to combat clinical manifestations. The natural history of this tumour is relatively long.

Overexpression of the human ubiquitin E3 ligase CUL4A alleviates hypoxia–reoxygenation injury in pheochromocytoma (PC12) cells

International Nuclear Information System (INIS)

Tan, Can; Zhang, Li-Yang; Chen, Hong; Xiao, Ling; Liu, Xian-Peng; Zhang, Jian-Xiang

2011-01-01

Highlights: ► Overexpression of human CUL4A (hCUL4A) in PC12 cells. ► The effects of hCUL4A on hypoxia–reoxygenation injury were investigated. ► hCUL4A suppresses apoptosis and DNA damage and thus promotes cell survival. ► hCUL4A regulates apoptosis-related proteins and cell cycle regulators. -- Abstract: The ubiquitin E3 ligase CUL4A plays important roles in diverse cellular processes including carcinogenesis and proliferation. It has been reported that the expression of CUL4A can be induced by hypoxic-ischemic injury. However, the effect of elevated expression of CUL4A on hypoxia–reoxygenation injury is currently unclear. In this study, human CUL4A (hCUL4A) was expressed in rat pheochromocytoma (PC12) cells using adenoviral vector-mediated gene transfer, and the effects of hCUL4A expression on hypoxia–reoxygenation injury were investigated. In PC12 cells subjected to hypoxia and reoxygenation, we found that hCUL4A suppresses apoptosis and DNA damage by regulating apoptosis-related proteins and cell cycle regulators (Bcl-2, caspase-3, p53 and p27); consequently, hCUL4A promotes cell survival. Taken together, our results reveal the beneficial effects of hCUL4A in PC12 cells upon hypoxia–reoxygenation injury.

Pheochromocytoma presenting as takotsubo-like cardiomyopathy following delivery.

Science.gov (United States)

Jóźwik-Plebanek, Katarzyna; Pęczkowska, Mariola; Klisiewicz, Anna; Wrzesiński, Kazimierz; Prejbisz, Aleksander; Niewada, Maciej; Kabat, Marek; Szperl, Małgorzata; Eisenhofer, Graeme; Lenders, Jacques W; Januszewicz, Andrzej

2014-12-01

Diagnosis of pheochromocytoma during pregnancy can be difficult, and the tumor carries an unfavorable prognosis if not diagnosed and treated in a timely manner. To present a case of Takotsubo-like cardiomyopathy characterized by transient left ventricular apical ballooning due to pheochromocytoma following delivery. A few hours after Caesarean section, a 32-year-old Caucasian female presented with pulmonary edema followed by cardiac arrest with echocardiographic and ventriculographic evidence of reversible acute myocardial failure characteristic of Takotsubo-like cardiomyopathy. A previously unrecognized adrenal pheochromocytoma was found during her clinical work-up. Left ventricle (LV) function normalized after surgical removal of the tumor, which was carried out after implementing an alpha-adrenoreceptor blockade. Hemorrhagic necrosis of the pheochromocytoma was seen on histopathologic analysis; this may have triggered the sequence of events leading to the development of Takotsubo-like cardiomyopathy and hemodynamic collapse. To the best of our knowledge, this is the first reported case of Takotsubo-like cardiomyopathy related to pheochromocytoma following delivery. This emphasizes the increased cardiovascular risk if pheochromocytoma is not diagnosed and treated in a timely manner, especially during pregnancy.

[About the signs of malignant pheochromocytoma].

Science.gov (United States)

Simonenko, V B; Makanin, M A; Dulin, P A; Vasilchenko, M I; Lesovik, V S

2012-01-01

Morphological criteria for malignant pheochromocytoma remain to be developed According to the WHO recommendations, the sole absolute criteria is the presence of metastases in the organs normally containing no chromaffin tissue. Such signs as cellular and nuclear polymorphism, mytotic activity, vascular invasion, capsular ingrowth are not sufficient to describe a pheochromocytoma as malignant. It is equally dfficult to differentiate between malignant and benign tumours based on histological data since histologically mature neoplasms can produce metastases. Based on the results of original studies, the authors believe that such histological features as vascular and capsular invasion do not necessarily suggest unfavourable prognosis. Therefore, the conclusion of malignancy based on such features can not be regarded as absolute. Probably such neoplasms should be called "pheochromocytomas with morphological signs of malignant growths". They should be referred to the tumours with uncertain malignancy potential based on the known discrepancy between morphological structure and biological activity of neoplasms. Comparative studies of clinical and morphological features of pheochromocytomas showed that their histological type (alveolar; solid, dyscomplexed, trabecular) and morphological signs of malignant growth influence both the clinical picture and arterial hypertension. There are no significant relationship between the above morphological signs, timour mass and clinical manifestations of pheochromocytomas.

Predictors of recurrence in pheochromocytoma.

Science.gov (United States)

Press, Danielle; Akyuz, Muhammet; Dural, Cem; Aliyev, Shamil; Monteiro, Rosebel; Mino, Jeff; Mitchell, Jamie; Hamrahian, Amir; Siperstein, Allan; Berber, Eren

2014-12-01

The recurrence rate of pheochromocytoma after adrenalectomy is 6.5-16.5%. This study aims to identify predictors of recurrence and optimal biochemical testing and imaging for detecting the recurrence of pheochromocytoma. In this retrospective study we reviewed all patients who underwent adrenalectomy for pheochromocytoma during a 14-year period at a single institution. One hundred thirty-five patients had adrenalectomy for pheochromocytoma. Eight patients (6%) developed recurrent disease. The median time from initial operation to diagnosis of recurrence was 35 months. On multivariate analysis, tumor size >5 cm was an independent predictor of recurrence. One patient with recurrence died, 4 had stable disease, 2 had progression of disease, and 1 was cured. Recurrence was diagnosed by increases in plasma and/or urinary metanephrines and positive imaging in 6 patients (75%), and by positive imaging and normal biochemical levels in 2 patients (25%). Patients with large tumors (>5 cm) should be followed vigilantly for recurrence. Because 25% of patients with recurrence had normal biochemical levels, we recommend routine imaging and testing of plasma or urinary metanephrines for prompt diagnosis of recurrence. Copyright © 2014 Elsevier Inc. All rights reserved.

Pheochromocytoma: a rare cause of childhood hypertensive encephalopathy

International Nuclear Information System (INIS)

Aftab, S.; Yasmeen, T.; Hamid, M.H.; Sarwar, M.; Sipra, H.; Sheikh, A.; Haider, N.; Hanif, G.

2012-01-01

Pheochromocytomas are rare neuroendocrine tumours of chromaffin tissues. They are catecholamine secreting tumours which cause severe hypertension and other systemic disturbances. Of all the causes of childhood hypertension, pheochromocytoma constitutes less than 1%. We report the case of a 12 years old child who presented with hypertensive encephalopathy, confirmed histologically to be secondary to pheochromocytoma, and cured with meticulous critical care and surgical resection. (author)

Nuclear medical diagnosis and therapy of pheochromocytoma

International Nuclear Information System (INIS)

Fischer, M.; Winterberg, B.; Vetter, H.; Mueller-Rensing, R.

1984-01-01

After prior labeling of the kidneys or the skeletal system for easier orientation, 0.3 - 0.7 mCi of I-131-MIBG (Henning-Berlin) were injected intravenously and scans were obtained with a gamma-camera-computer system 24 to 120 hours later. 22 patients showed clinical and biochemical evidence of pheochromocytoma; the diagnosis was confirmed surgically in 19. Two patients (16 years old) with metastatic pheochromocytoma and a female aged 73 years with intra-adrenal pheochromocytoma ineligible for surgery because of catecholamine-induced myocarditis currently undergo fractionated I-131-MIBG treatment with single doses of 65 - 135 mCi. The tumor response was assessed in 2 females by determining the volume of reference tumors with computer tomography; by 24-hour urinary catecholamine assays; and by checking drug consumption. Scintigraphy showed intra-adrenal pheochromocytoma to be present in 17 cases (left, n=11; right, n=5; bilateral, n=1). Two patients were found to have medullary hyperplasia, while 3 presented with multilocular malignant pheochromocytoma. Treatment substantially improved the clinical symptoms in 3 females. Determination of tumor volume by computer tomography showed a tumor reduction of 61% in 1 patient after a total dose of 415 mCi and of 10% after a total dose of 365 mCi in another patient. Experiences sofar available suggest that I-131-MIBG is a useful specific radionuclide for the diagnosis and treatment of pheochromocytoma. (Author)

Overexpression of the human ubiquitin E3 ligase CUL4A alleviates hypoxia-reoxygenation injury in pheochromocytoma (PC12) cells

Energy Technology Data Exchange (ETDEWEB)

Tan, Can [Department of Histology and Embryology, School of Basic Medical Sciences, Central South University, 172 Tong Zipo Road, Changsha 410013 (China); Zhang, Li-Yang [Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, 110 Xiang Ya Road, Changsha 410078 (China); Chen, Hong [Department of Developmental Biology, School of Biological Science and Technology, Central South University, 172 Tong Zipo Road, Changsha 410013 (China); Xiao, Ling [Department of Histology and Embryology, School of Basic Medical Sciences, Central South University, 172 Tong Zipo Road, Changsha 410013 (China); Liu, Xian-Peng, E-mail: xliu@lsuhsc.edu [Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130-3932 (United States); Zhang, Jian-Xiang, E-mail: jianxiangzhang@yahoo.cn [Department of Histology and Embryology, School of Basic Medical Sciences, Central South University, 172 Tong Zipo Road, Changsha 410013 (China); Department of Developmental Biology, School of Biological Science and Technology, Central South University, 172 Tong Zipo Road, Changsha 410013 (China)

2011-12-16

Highlights: Black-Right-Pointing-Pointer Overexpression of human CUL4A (hCUL4A) in PC12 cells. Black-Right-Pointing-Pointer The effects of hCUL4A on hypoxia-reoxygenation injury were investigated. Black-Right-Pointing-Pointer hCUL4A suppresses apoptosis and DNA damage and thus promotes cell survival. Black-Right-Pointing-Pointer hCUL4A regulates apoptosis-related proteins and cell cycle regulators. -- Abstract: The ubiquitin E3 ligase CUL4A plays important roles in diverse cellular processes including carcinogenesis and proliferation. It has been reported that the expression of CUL4A can be induced by hypoxic-ischemic injury. However, the effect of elevated expression of CUL4A on hypoxia-reoxygenation injury is currently unclear. In this study, human CUL4A (hCUL4A) was expressed in rat pheochromocytoma (PC12) cells using adenoviral vector-mediated gene transfer, and the effects of hCUL4A expression on hypoxia-reoxygenation injury were investigated. In PC12 cells subjected to hypoxia and reoxygenation, we found that hCUL4A suppresses apoptosis and DNA damage by regulating apoptosis-related proteins and cell cycle regulators (Bcl-2, caspase-3, p53 and p27); consequently, hCUL4A promotes cell survival. Taken together, our results reveal the beneficial effects of hCUL4A in PC12 cells upon hypoxia-reoxygenation injury.

Metastatic pheochromocytoma in an 18-year-old

Directory of Open Access Journals (Sweden)

Ali Cadili

2016-03-01

Full Text Available Pheochromocytoma most commonly presents with a combination of headache, sweating, and hypertension. This case report reviews the case of a young male patient presenting with hypertensive crisis following administration of general anesthetics and who was subsequently diagnosed with malignant pheochromocytoma. Up to date, no reliable predictive factors for malignant pheochromocytoma have been established. This case emphasizes the need for a systematic approach to the hypertensive crisis and advantages of nuclear imaging to differentiate benign from malignant disease through detection of local invasion and distant metastases. [Arch Clin Exp Surg 2016; 5(1.000: 48-51

Pheochromocytoma during Pregnancy

Science.gov (United States)

... foods high in tyramine (such as red wine, chocolate, and cheese). Tests that examine the blood and ... cause signs or symptoms are treated with drug therapy. Drug therapy begins when pheochromocytoma or paraganglioma is ...

Pheochromocytoma and gastrointestinal stromal tumors in patients with neurofibromatosis type I.

Science.gov (United States)

Vlenterie, Myrella; Flucke, Uta; Hofbauer, Lorenz C; Timmers, Henri J L M; Gastmeier, Joerg; Aust, Daniela E; van der Graaf, Winette T A; Wesseling, Pieter; Eisenhofer, Graeme; Lenders, Jacques W M

2013-02-01

Neurofibromatosis I may rarely predispose to pheochromocytoma and gastrointestinal stromal tumors. A 59-year-old woman with neurofibromatosis I presented with pheochromocytoma of the left adrenal gland. During surgery, 3 gastrointestinal stromal tumors adjacent to the stomach and small intestine were removed. Despite appropriate thrombosis prophylaxis, the patient died of a pulmonary embolus 2 days postoperatively. The second patient, a 55-year-old man with neurofibromatosis I and bilateral pheochromocytomas, had several small gastrointestinal stromal tumors adjacent to the jejunum during surgery. A review of the literature was conducted to identify patients with neurofibromatosis I with concurrence of pheochromocytoma and gastrointestinal stromal tumors and to define the specific clinical features of these patients. In addition to our 2 patients, 12 other cases of neurofibromatosis I with concomitant occurrence of pheochromocytomas and gastrointestinal stromal tumors have been reported. Pheochromocytomas had adrenal locations in all patients. Two of the 14 patients had a mixed pheochromocytoma/ganglioneuroma. In 4 of the 14 patients, gastrointestinal stromal tumors were located along the stomach. The gastrointestinal stromal tumors in our 2 patients showed no somatic mutations in KIT and PDGFRA genes. A pulmonary embolism was diagnosed in 4 patients. The simultaneous occurrence of pheochromocytoma and gastrointestinal stromal tumor should be considered in all patients with neurofibromatosis I presenting with an abdominal mass with symptoms suggestive of pheochromocytoma. Therefore, a pheochromocytoma should be excluded before a patient with neurofibromatosis I undergoes surgery for a gastrointestinal stromal tumor because an undiagnosed pheochromocytoma carries a high risk of life-threatening cardiovascular complications during surgery. Finally, this combination may be associated with an increased risk for thromboembolic events, but more studies are necessary to

Effects of Aroclor 1254 on dopamine and norepinephrine concentrations in pheochromocytoma (PC-12) cells

International Nuclear Information System (INIS)

Seegal, R.F.; Brosch, K.; Bush, B.; Ritz, M.; Shain, W.

1990-01-01

Pheochromocytoma (PC-12) cells synthesize, store, release and metabolize dopamine (DA) and norepinephrine (NE) in a manner analogous to that observed in the mammalian central nervous system. These cells were used to develop and validate an alternate method to animal testing to assess the effects of a complex environmental mixture of polychlorinated biphenyls (Aroclor 1254) on cellular catecholamine function. Aroclor 1254, at concentrations of 1 to 100 ppm, significantly decreased cellular catecholamine concentrations after 6 hrs. Exposure at 100 ppm for periods of less than an hr increased cellular catecholamine concentrations while longer exposure times (i.e., 1 to 24 hr) decreased cellular catecholamine concentrations. This in vitro depletion of catecholamines is similar to that seen in vivo. Thus, PC-12 cells may be useful for neurochemical evaluation of neurotoxicants with particular reference to effects on catecholaminergic systems

Coexistence of pheochromocytoma with uncommon vascular lesions

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Sunil Kumar Kota

2012-01-01

Full Text Available Background: Pheochromocytoma/paragangliomas have been described to be associated with rare vascular abnormalities like renal artery stenosis. Coexistence of physiologically significant renal artery lesions is a compounding factor that alters management and prognosis of pheochromocytoma patients. Apart from individual case reports, data on such association in Indian population is not available. The aim of this study is to find the nature and prevalence of associated vascular abnormalities. Materials and Methods: From 1990 to 2010, a total of 50 patients were diagnosed with pheochromocytoma/paragangliomas. Hospital charts of these patients were reviewed retrospectively to identify those with unusual vascular abnormalities. Available literature was also reviewed. Results: Of the 50 patients with pheochromocytoma, 7 (14% had coexisting vascular lesions including renal artery stenosis in 4, aortoarteritis in 1, aortic aneurysm in 1 and inferior vena cava thrombosis in 1. Pheochromocytoma was adrenal in 42 and extra adrenal in 8. Laparoscopic adrenalectomy was done in the patients. One patient with renal artery stenosis due to intimal fibrosis was subjected to percutaneous balloon angioplasty; the other three improved after adrenalectomy and lysis of fibrous adhesive bands. The patient with aortoarteritos was treated with oral steroids. Inferior vena cava thrombosis was reversed with anticoagulants. The patient with abdominal aortic aneurysm was advised for annual follow-up on account of its size of 4.5 cm and asymptomatic presentation. Conclusion: There are multiple mechanisms that can lead to renal artery stenosis and other vascular abnormalities in a case of pheochromocytoma. A high index of suspicion is necessary to enable both entities to be diagnosed preoperatively and allow proper planning of surgical therapy. Incomplete diagnosis may lead to persistent hypertension postoperatively in a case of associated renal artery stenosis.

Pheochromocytoma in pregnancy: Case report | Ogutu | East African ...

African Journals Online (AJOL)

This is a case presentation of a 32 year old woman with pheochromocytoma diagnosed at 27 weeks of gestation, she was managed till term, induced and had assisted vaginal delivery. The pheochromocytoma was surgically re-sected successfully at six weeks postpartum.

Pheochromocytoma with Markedly Abnormal Liver Function Tests and Severe Leukocytosis

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Chai Ryoung Eun

2014-03-01

Full Text Available Pheochromocytoma is a rare neuroendocrine tumor arising from the medulla of the adrenal glands, which causes an overproduction of catecholamines. The common symptoms are headache, palpitations, and sweating; however, various other clinical manifestations might also be present. Accurate diagnosis of pheochromocytoma is important because surgical treatment is usually successful, and associated clinical problems are reversible if treated early. A 49-year-old man with a history of uncontrolled hypertension and diabetes mellitus presented with chest pain, fever, and sweating. His liver function tests and white blood cell counts were markedly increased and his echocardiography results suggested stress-induced cardiomyopathy. His abdominal computed tomography showed a 5×5-cm-sized tumor in the left adrenal gland, and laboratory tests confirmed catecholamine overproduction. After surgical resection of the left adrenal gland, his liver function tests and white blood cell counts normalized, and echocardiography showed normal cardiac function. Moreover, his previous antihypertensive regimen was deescalated, and his previously uncontrolled blood glucose levels normalized without medication.

Graves′ disease allied with multiple pheochromocytoma

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Brahim Housni

2013-01-01

Full Text Available Pheochromocytoma is an uncommon cause of high blood pressure touching adults. The combination of severe hypertension in the triad of headache, sweating, and tachycardia should suggest this diagnosis; this clinical picture is similar to that of hyperthyroidism. We report the case of a 22-year-old patient with multiple pheochromocytoma associated with Graves′ disease revealed by malignant hypertension and discussed the difficulties of the diagnosis and the treatment approach.

A UNIQUE CASE OF PHEOCHROMOCYTOMA PRESENTING WITH HYPERTENSIVE RETINOPATHY

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Maji.S, Saha. ML, Kanwar KS, Das S, Bhagat P, Bhar P

2015-04-01

Full Text Available ABSTRACT Pheochromocytoma is an extremely uncommon tumor of childhood and there are several features that distinguish its presentation between adults and children. The incidence of pheochromocytoma in childhood is 10% of the adult incidence, occurring in approximately 1 in 500,000 children compared with 1 in 50,000 adults. Around 10% of childhood tumors are familial which is 4times the frequency in adults. Whereas only 7% of pheochromocytomas are bilateral in adults, the reported incidence of the same in children range from 24 % to as high as &70%.These tumors are known for their great diversity in clinical presentation. Greater than 50% of children present with headaches, fever, palpitation, thirst, polyuria, sweating, nausea and weight loss. However the commonest mode of presentation is sustained hypertension. Pheochromocytoma accounts for 0.5% of children with hypertension and must be considered once other causes have been eliminated. We here in report a unique case of a 13 year old girl who initially presented with bilateral hypertensive retinopathy and later found to have a pheochromocytoma on subsequent workup. Hypertensive retinopathy secondary to pheochromocytoma is itself a rare entity whose exact incidence in children is still unknown. This case highlights the importance of routine history, physical examination and measurement of bp. Prompt surgery can reverse the effect of hypertension and lead to good outcome as was evident in our case.

Pheochromocytomas and secreting paragangliomas

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Gimenez-Roqueplo Anne-Paule

2006-12-01

Full Text Available Abstract Catecholamine-producing tumors may arise in the adrenal medulla (pheochromocytomas or in extraadrenal chromaffin cells (secreting paragangliomas. Their prevalence is about 0.1% in patients with hypertension and 4% in patients with a fortuitously discovered adrenal mass. An increase in the production of catecholamines causes symptoms (mainly headaches, palpitations and excess sweating and signs (mainly hypertension, weight loss and diabetes reflecting the effects of epinephrine and norepinephrine on α- and β-adrenergic receptors. Catecholamine-producing tumors mimic paroxysmal conditions with hypertension and/or cardiac rhythm disorders, including panic attacks, in which sympathetic activation linked to anxiety reproduces the same signs and symptoms. These tumors may be sporadic or part of any of several genetic diseases: familial pheochromocytoma-paraganglioma syndromes, multiple endocrine neoplasia type 2, neurofibromatosis 1 and von Hippel-Lindau disease. Familial cases are diagnosed earlier and are more frequently bilateral and recurring than sporadic cases. The most specific and sensitive diagnostic test for the tumor is the determination of plasma or urinary metanephrines. The tumor can be located by computed tomography, magnetic resonance imaging and metaiodobenzylguanidine scintigraphy. Treatment requires resection of the tumor, generally by laparoscopic surgery. About 10% of tumors are malignant either at first operation or during follow-up, malignancy being diagnosed by the presence of lymph node, visceral or bone metastases. Recurrences and malignancy are more frequent in cases with large or extraadrenal tumors. Patients, especially those with familial or extraadrenal tumors, should be followed-up indefinitely.

Spontaneous adrenal pheochromocytoma rupture complicated by intraperitoneal hemorrhage and shock

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Kwasnik Edward

2011-08-01

Full Text Available Abstract MEN2A is a hereditary syndrome characterized by medullary thyroid carcinoma, hyperparathyroidism, and pheochromocytoma. Classically patients with a pheochromocytoma initially present with the triad of paroxysmal headaches, palpitations, and diaphoresis accompanied by marked hypertension. However, although reported as a rare presentation, spontaneous hemorrhage within a pheochromocytoma can present as an abdominal catastrophe. Unrecognized, this transformation can rapidly result in death. We report the only documented case of a thirty eight year old gentleman with MEN2A who presented to a community hospital with hemorrhagic shock and peritonitis secondary to an unrecognized hemorrhagic pheochromocytoma. The clinical course is notable for an inability to localize the source of hemorrhage during an initial damage control laparotomy that stabilized the patient sufficiently to allow emergent transfer to our facility, re-exploration for continued hemorrhage and abdominal compartment syndrome, and ultimately angiographic embolization of the left adrenal artery for control of the bleeding. Following recovery from his critical illness and appropriate medical management for pheochromocytoma, he returned for interval bilateral adrenal gland resection, from which his recovery was unremarkable. Our review of the literature highlights the high mortality associated with the undertaking of an operative intervention in the face of an unrecognized functional pheochromocytoma. This reinforces the need for maintaining a high index of suspicion for pheochromocytoma in similar cases. Our case also demonstrates the need for a mutimodal treatment approach that will often be required in these cases.

Review of Pediatric Pheochromocytoma and Paraganglioma

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Reshma Bholah

2017-07-01

Full Text Available Pheochromocytoma (PCC and paraganglioma (PGL are rare chromaffin cell tumors which secrete catecholamines and form part of the family of neuroendocrine tumors. Although a rare cause of secondary hypertension in pediatrics, the presentation of hypertension in these patients is characteristic, and treatment is definitive. The gold standard for diagnosis is via measurement of plasma free metanephrines, with imaging studies performed for localization, identification of metastatic lesions and for surgical resection. Preoperative therapy with alpha-blocking agents, beta blockers, and potentially tyrosine hydroxylase inhibitors aid in a safe pre-, intra- and postoperative course. PCC and PGL are inherited in as much as 80% of pediatric cases, and all patients with mutations should be followed closely given the risk of recurrence and malignancy. While the presentation of chromaffin cell tumors has been well described with multiple endocrine neoplasia, NF1, and Von Hippel–Lindau syndromes, the identification of new gene mutations leading to chromaffin cell tumors at a young age is changing the landscape of how clinicians approach such cases. The paraganglioma–pheochromocytoma syndromes (SDHx comprise familial gene mutations, of which the SDHB gene mutation carries a high rate of malignancy. Since the inheritance rate of such tumors is higher than previously described, genetic screening is recommended in all patients, and lifelong follow-up for recurrent tumors is a must. A multidisciplinary team approach allows for optimal health-care delivery in such children. This review serves to provide an overview of pediatric PCC and PGL, including updates on the preferred methods of imaging, guidelines on gene testing as well as management of hypertension in such patients.

Primary hepatic pheochromocytoma

International Nuclear Information System (INIS)

Rimmelin, A.; Hartheiser, M.; Gangi, A.; Welsch, M.; Jeung, M.Y.; Jaeck, D.; Tongio, J.; Dietemann, J.L.

1996-01-01

Pheochromocytomas are uncommon tumors that represent a potentially curable cause of hypertension. They are usually located in the adrenal glands, but 10% arise from extra-adrenal sites, located along the paravertebral sympathetic chains. We report a case of primary hepatic pheochromocytoma responsible for a severe hypertension in a 24-year-old man. Echotomography showed a lightly heterogeneous mass located in the segment 8 of the liver. Iodine 131 -metaiodobenzylguanidine scintigraphy showed a large hepatic concentration of the tracer and no other localization. This tumor appeared highly vascularized on enhanced CT scan and on aortic angiography. Magnetic resonance imaging revealed a hepatic tumor with a high signal intensity on T2-weighted images and with a signal isointense to the liver on T1-weighted images. The hepatic venous sampling contained the highest catecholamine level, whereas the adrenal venous samping was normal. After surgical resection of the hepatic tumor, the tension level and catecholamines plasmatic level normalized. No recurrent symptoms appeared during a 3-year follow-up. (orig.)

THE PHYSIOLOGY BEHIND DIABETES MELLITUS IN PATIENTS WITH PHEOCHROMOCYTOMA: A REVIEW OF THE LITERATURE.

Science.gov (United States)

Mesmar, Bayan; Poola-Kella, Silpa; Malek, Rana

2017-08-01

This paper reviews the physiologic mechanisms responsible for glucose intolerance and diabetes mellitus in patients with pheochromocytoma. Google Scholar and PubMed were searched using the following key words: "diabetes," "pheochromocytoma," "adrenoreceptors," and "hyperglycemia." All the articles that were retrieved and reviewed were in the English language. Glucose intolerance and diabetes mellitus, resulting from high circulating levels of catecholamines, are mainly the product of compromised insulin secretion from the β-cells in the pancreas, decreased glucose uptake in the peripheral tissues, and increased insulin resistance. As pheochromocytomas mainly present with cardiovascular and autonomic hyperfunctioning, it is important to understand the metabolic disorders associated with this rare disease. Hyperglycemia is an associated metabolic abnormality which can drastically improve after tumor resection, and significant downscaling of anti-hyperglycemic therapy is often required. GLUT4 = glucose transporter type 4 HbA1c = hemoglobin A1c IL = interleukin OGTT = oral glucose tolerance test.

Von Hippel-Lindau Syndrome: Diagnosis and Management of Hemangioblastoma and Pheochromocytoma

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P. Vaganovs

2013-01-01

Full Text Available Introduction. Von Hippel-Lindau (VHL syndrome is a pathological condition that causes various clinical symptoms and is difficult to diagnose. The most common pathological lesions are hemangioblastomas of the central nervous system, retinal angiomas, renal clear cell carcinomas, and pheochromocytomas. Case Report. A 23-year-old female had a syncope episode in 2008. Magnetic resonance imaging (MRI revealed a right temporal hemangioblastoma, which was treated surgically. Genetic screening identified a VHL gene mutation, and computed tomography (CT revealed a left adrenal mass. Since it was unclear whether the mass was a pheochromocytoma, or another benign or malignant tumors, laparoscopic adrenalectomy was performed. A month after surgery, the patient complained of general fatigue, poor concentration, loss of appetite, and insomnia. After careful clinical investigation, the patient was referred to a psychiatrist due to suspected depression, which was confirmed. Conclusions. VHL genetic screening should be performed in cases of hemangioblastoma. In VHL syndrome cases, pheochromocytoma cannot always be diagnosed by biochemical catecholamine analyses; therefore, CT or MRI scanning of the abdomen must be performed. Due to the long treatment period, some patients may develop episodes of depression, which can simulate VHL syndrome.

Low sensitivity of glucagon provocative testing for diagnosis of pheochromocytoma.

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Lenders, Jacques W M; Pacak, Karel; Huynh, Thanh-Truc; Sharabi, Yehonatan; Mannelli, Massimo; Bratslavsky, Gennady; Goldstein, David S; Bornstein, Stefan R; Eisenhofer, Graeme

2010-01-01

Pheochromocytomas can usually be confirmed or excluded using currently available biochemical tests of catecholamine excess. Follow-up tests are, nevertheless, often required to distinguish false-positive from true-positive results. The glucagon stimulation test represents one such test; its diagnostic utility is, however, unclear. The aim of the study was to determine the diagnostic power of the glucagon test to exclude or confirm pheochromocytoma. Glucagon stimulation tests were carried out at three specialist referral centers in 64 patients with pheochromocytoma, 38 patients in whom the tumor was excluded, and in a reference group of 36 healthy volunteers. Plasma concentrations of norepinephrine and epinephrine were measured before and after glucagon administration. Several absolute and relative test criteria were used for calculating diagnostic sensitivity and specificity. Expression of the glucagon receptor was examined in pheochromocytoma tumor tissue from a subset of patients. Larger than 3-fold increases in plasma norepinephrine after glucagon strongly predicted the presence of a pheochromocytoma (100% specificity and positive predictive value). However, irrespective of the various criteria examined, glucagon-provoked increases in plasma catecholamines revealed the presence of the tumor in less than 50% of affected patients. Diagnostic sensitivity was particularly low in patients with pheochromocytomas due to von Hippel-Lindau syndrome. Tumors from these patients showed no significant expression of the glucagon receptor. The glucagon stimulation test offers insufficient diagnostic sensitivity for reliable exclusion or confirmation of pheochromocytoma. Because of this and the risk of hypertensive complications, the test should be abandoned in routine clinical practice.

Extra-adrenal Pheochromocytoma in an Adolescent

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Abdullah, Ibrahim

2011-05-01

Full Text Available A 17-year-old male with symptoms of headache and diaphoresis presented to the emergency department. He had eight months of noted hypertension attributed to medications. On arrival his blood pressure was 229/117mmHg, and he was ill-appearing. His blood pressure was managed aggressively, and he was diagnosed with extra-adrenal pheochromocytoma by computed tomography. He eventually underwent resection of the mass. Children with severe, symptomatic hypertension should be evaluated for pheochromocytoma. Although rare, it is curable. Failure to diagnose carries a high risk of morbidity and mortality. [West J Emerg Med. 2011;12(2:258-261.

Adrenocorticotropic hormone-producing pheochromocytoma: analysis of clinical cases

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Evgeniya Ivanovna Marova

2015-04-01

Full Text Available Ectopic secretion of ACTH from non-pituitary tumors, referred to as ectopic ACTH syndrome (EAS, accounts for about 10–20% of Cushing’s syndrome (CS. Ectopic hormone-secreting pheochromocytomas (Pheo are rare. The first publication of association between pheochromocytoma and Cushing’s syndrome by Roux is dated 1955. Pheochromocytoma represents a rare cause of hypercortisolism, accounting for less than 5 % of ectopic Cushing’s syndrome while less than 1 % of pheochromocytomas is accompanied by Cushing’s syndrome. We are reporting 4 cases of ACTH-secreting pheochromocytoma presenting as Cushing’s syndrome. Data from 4 patients were analysed. There were 4 women from 50 to 63 years old. All patients had a clinical presentation of hypercorticoidism. Their levels of adrenocorticotropic hormone in plasma, 24-hour urinary free cortisol and urinary catecholamine were high. Computed tomography scan of the abdomen in all cases revealed a mass in the left adrenal gland. Left sided adrenalectomy was performed under treatment with a-blocker doxazosin and b-blocker atenolol. Histological examination revealed in 3 cases – pheocromocytoma and in 1 case corticomedullary mixed tumor of the adrenal gland. Additional immunostaining (IHCof these tumors showed positive immunostaining for chromogranin and ACTH. The IHC search for somatostatin receptors of subtype 2 and 5 (SSTR2, SSTR5 was performed in 3 cases and showed predominately expression SSTR2. The case index of Ki-67 ranged, from 0,5 to 4%. Biochemical signs of hypercortisolism rapidly began to disappear after surgery. Follow up of the patients during the next 2 years on average was with disease remission.

Introduction of a Case of Bilateral Pheochromocytoma Tumor

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M Zare

2009-01-01

Full Text Available Summary: Pheochromocytoma is an adrenal tumor characterized by symptoms of hypertension, headache, increased sweating, and tachycardia .In one third of patients, the tumor is discovered incidentally during radiological evaluation of the abdomen. In this article a case of bilateral pheochromocytoma is reported. The patient, a twelve years old boy, referred with complaints of headache, flushing, palpitation and blurring of vision. He had a blood pressure of 200/120 mmHg and after investigation, coarctation of aorta was excluded. On abdominal ultrasound, bilateral adrenal mass was diagnosed, followed by serial measurements of urinary vanillyl mandellic acid (VMA which was found to be elevated. Meta- Iodio benzyl glunidin (MIBG scan showed increased uptake in both adrenals. Patient underwent laparotomy and bilateral adrenalectomy with the diagnosis of pheochromocytoma. Pathologic report confirmed the diagnosis

The Epidemiology of Pheochromocytoma

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Ladefoged Ebbehøj, Andreas

2017-01-01

Pheochromocytoma and catecholamine secreting paraganglioma (PPGL) are exceedingly rare endocrine tumours, but remain a frequent diagnostic dilemma due to their potential life-threatening nature. Reliable data on the epidemiology of PPGL is lacking and no time trends in incidence rates (IR) have...

131I-MIBG Scintigraphy in the Evaluation of Suspected Pheochromocytoma

International Nuclear Information System (INIS)

Oh, Sei Jung; Yoo, Hyung Sik; Park, Chang Yun; Lee, So Jin

1992-01-01

Pheochromocytomas are catecholamine producing tumors of neuroectodermal origin. Diagnosis of pheochromocytoma is significant due to potentially curable hypertension. But they have a significant associated morbidity due to uncontrolled hypertension and mortality since 10% are malignant. From Aug. 1989 to Jul. 1992, 12 patients of our institution had 131 I-MIBG scan during work up of suspected primary or recurrent pheochromocytoma. In our studies conclude that 131 I-MIBG scan is recommended as the initial localizing study of choice (especially for the detection of extraadrenal disease and postoperative recurrence) as a guide for CT and/or MR and specific functional confirmation of their findings.

Stages of Pheochromocytoma and Paraganglioma

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... foods high in tyramine (such as red wine, chocolate, and cheese). Tests that examine the blood and ... cause signs or symptoms are treated with drug therapy. Drug therapy begins when pheochromocytoma or paraganglioma is ...

Concurrent primary hyperparathyroidism and pheochromocytoma in a Chinese lady with neurofibromatosis type 1

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Cheuk-Lik Wong

2018-04-01

Full Text Available We report a case of elderly Chinese lady with neurofibromatosis type-1 presenting with longstanding palpitation, paroxysmal hypertension and osteoporosis. Biochemical testing showed mild hypercalcaemia with non-suppressed parathyroid hormone level suggestive of primary hyperparathyroidism, and mildly elevated urinary fractionated normetanephrine and plasma-free normetanephrine pointing to a catecholamine-secreting pheochromocytoma/paraganglioma. Further scintigraphic investigation revealed evidence of a solitary parathyroid adenoma causing primary hyperparathyroidism and a left pheochromocytoma. Resection of the parathyroid adenoma and pheochromocytoma resulted in normalization of biochemical abnormalities and hypertension. The rare concurrence of primary hyperparathyroidism and pheochromocytoma in neurofibromatosis type-1 is discussed.

Pheochromocytoma and pregnancy: A case report and review.

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Santos, Davi Rettori Pardo Dos; Barbisan, Cinthia Callegari; Marcellini, Claudio; dos Santos, Rubia Marina Vieira Rettori

2015-01-01

Pheochromocytoma is a catecholamine-producing adrenal tumor, being a rare cause of hypertension in pregnancy. It's prevalence in hypertensive patients is 0.2%, and 0.002% of pregnancies. We follow hypertensive pregnant 24 year old on her third pregnancy, admitted to 33 weeks with hypertensive emergency cesarean section indicated by fetal distress evolving with acute pulmonary edema in the post-partum period. Indicated laparoscopy after 13 days for acute abdominal pain, with no significant finding. In the postoperative, due a severe and resistant hypertension, suspected of pheochromocytoma and confirmed by biochemical tests and imaging. Performed unilateral adrenelectomia with cure of hypertension. The pathology and immunohistochemistry confirmed the diagnosis. We conclude that atypical cases of hypertension in pregnancy should be investigated early and differentiated pre-eclampsia. Despite the low prevalence, pheochromocytoma in pregnancy increases fetal maternal morbidity and mortality and the early recognition and treatment drastically change their outcome.

A patient with bilateral pheochromocytoma as part of a Von Hippel-Lindau (VHL syndrome type 2C

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Rinkes Inne

2007-10-01

Full Text Available Abstract Background Von Hippel-Lindau (VHL disease is an autosomal dominant inherited disease. It is relatively recent that type 2C was identified as a separate group solely presenting with pheochromocytomas. As an illustration, an interesting case is presented of a pregnant woman with refractory hypertension. It proved to be the first manifestation of bilateral pheochromocytomas. The family history may indicate the diagnosis, but only identification of a germ line mutation in the DNA of a patient will confirm carriership. Case presentation A 27 year pregnant patient with intra uterine growth retardation presented with hypertension and pre-eclampsia. Magnetic resonance imaging revealed bilateral adrenal pheochromocytoma. She underwent laparoscopic adrenelectomy and a missense mutation (Gly93Ser in exon 1 of the VHL gene on chromosome 3 (p25 – p26 was shown in the patient, her father and her daughter confirming the diagnosis of VHL. Conclusion In almost all VHL families molecular genetic analysis of DNA will demonstrate an inherited mutation. Because of the involvement in several organs, periodic clinical evaluation should take place in a well coordinated, multidisciplinary setting. VHL disease can be classified into several subtypes. VHL type 2C patients present with pheochromocytomas without evidence of haemangioblastomas in the central nervous system and/or retina and a low risk of renal cell carcinoma. Therefore, in such families, periodic clinical screening can be focussed on pheochromocytomas.

Watery diarrhea syndrome in an adult with ganglioneuroma-pheochromocytoma: identification of vasoactive intestinal peptide, calcitonin, and catecholamines and assessment of their biologic activity.

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Trump, D L; Livingston, J N; Baylin, S B

1977-10-01

A case of adult ganglioneuroma-pheochromocytoma with an associated watery diarrhea syndrome is reported. High levels of vasoactive intestinal peptide (VIP) were found in preoperative serum and in tumor tissue. The serum VIP levels fell to normal, and the watery diarrhae syndrome completely ceased following removal of the tumor. In addition to containing VIP, the tumor was rich in catecholamines, and calcitonin. Peptide hormone-containing extracts and catecholamine extracts from the tumor both activated the adenyl cyclase system and increased lipolytic activity in a preparation of isolated rat fat cells. The findings in this patient further link VIP with neural crest tissues, and suggest the importance of determining catecholamine levels in patients with the watery diarrhea syndrome.

Severe posterior reversible encephalopathy in pheochromocytoma: Importance of susceptibility-weighted MRI

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Serter, Asil; Alkan, Alpay; Aralasmak, Ayse; Kocakoc, Ercan [Dept. of Radiology, Bezmialem Vakif University School of Medicine, Istanbul (Turkmenistan)

2013-10-15

Pheochromocytoma is a rare cause of hypertension in children. Hypertension is one of the common reasons of posterior reversible encephalopathy. Intracerebral hemorrhage is a serious and unexpected complication of hypertensive encephalopathy due to pheochromocytoma, and very rarely seen in the childhood. Intracerebral hemorrhages should be searched if there are hypertensive reversible signal changes on the brain. Susceptibility weighted imaging (SWI) is a more sensitive method than conventional MRI when demonstrating cerebral microhemorrhagic foci. This is the first report of SWI findings on intracerebral hemorrhages in basal ganglia, brain stem and periventricular white matter due to hypertensive encephalopathy in a child with pheochromocytoma.

Spontaneous rupture of pheochromocytoma and its clinical features: a case report.

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Maruyama, Mayumi; Sato, Haruhiro; Yagame, Mitsunori; Shoji, Sunao; Terachi, Toshiro; Osamura, Robert Yoshiyuki

2008-09-20

Rupture of adrenal pheochromocytoma is extremely rare and can be lethal because of dramatic changes in the circulation. We describe a 58-year-old Japanese man who suffered rupture of a pheochromocytoma. The patient was referred to our hospital because of severe hypertension (256/127 mmHg) and a left adrenal tumor. T2-weighted magnetic resonance imaging showed high signal intensity in the 50-mm left adrenal tumor. Endocrinological examinations showed elevated plasma and urinary catecholamine levels. These findings suggested that the left adrenal tumor was a pheochromocytoma. Phentolamine mesilate was administered intravenously. This resulted in a decrease of the systolic blood pressure to 100 mmHg. On the third hospital day, the patient complained of left back pain, and abdominal computed tomography showed rupture of the pheochromocytoma. Pulmonary congestion and effusion, and paralytic small-intestinal ileus occurred. Blood pressure was controlled, small-intestinal decompression was done with a Miller-Abbot tube, and body water was controlled by fluid replacement. After the general condition of the patient had became stable, laparoscopic adrenalectomy was performed. Phentolamine mesilate is a useful α-adrenergic blocker. However, care is needed with its administration, because rupture of pheochromocytoma may be related to a decrease in blood pressure induced by phentolamine mesilate.

[Acute cardiac failure in pheochromocytoma.

DEFF Research Database (Denmark)

Jønler, Morten; Munk, Kim

2008-01-01

Pheochromocytoma (P) is an endocrine catecholamine-secreting tumor. Classical symptoms like hypertension, attacks of sweating, palpitations, headache and palor are related to catecholamine discharge. We provide a case of P in a 71 year-old man presenting with acute cardiac failure, severe reduction...

Marker-Negative Pheochromocytoma Associated with Inferior Vena Cava Thrombosis

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S. Poudyal

2017-01-01

Full Text Available Pheochromocytoma associated with inferior vena cava (IVC thrombosis is very rare. A 27-year-old female presented with right flank pain and hypertensive urgency. Contrast-enhanced CT abdomen and gadolinium-contrast MRI abdomen revealed right adrenal mass suspicious of malignancy with invasion and compression to the right IVC wall along with IVC thrombus extending from the level of renal veins to the level of confluence with hepatic veins. Her routine laboratory investigations including 24-hour urine fractionated metanephrines, vanillylmandelic acid, and cortisol were normal. Right adrenalectomy with IVC thrombectomy was done. Perioperative period was uneventful. Histopathology of the mass turned out to be pheochromocytoma with thrombus revealing fibroadipose tissue with fibrin. Pheochromocytoma may present with IVC thrombus as well as normal serum and urinary markers. Thus, clinical suspicion is imperative in perioperative management of adrenal mass.

High Sensitive and Selective Sensing of Hydrogen Peroxide Released from Pheochromocytoma Cells Based on Pt-Au Bimetallic Nanoparticles Electrodeposited on Reduced Graphene Sheets

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Guangxia Yu

2015-01-01

Full Text Available In this study, a high sensitive and selective hydrogen peroxide (H2O2 sensor was successfully constructed with Pt-Au bimetallic nanoparticles (Pt-Au NPs/reduced graphene sheets (rGSs hybrid films. Various molar ratios of Au to Pt and different electrodeposition conditions were evaluated to control the morphology and electrocatalytic activity of the Pt-Au bimetallic nanoparticles. Upon optimal conditions, wide linear ranges from 1 µM to 1.78 mM and 1.78 mM to 16.8 mM were obtained, with a detection limit as low as 0.31 µM. Besides, due to the synergetic effects of the bimetallic NPs and rGSs, the amperometric H2O2 sensor could operate at a low potential of 0 V. Under this potential, not only common anodic interferences induced from ascorbic acid, uric acid and dopamine, but also the cathodic interference induced from endogenous O2 could be effectively avoided. Furthermore, with rat pheochromocytoma cells (PC 12 as model, the proposed sensor had been successfully used in the detection of H2O2 released from the cancer cells. This method with wide linear ranges and excellent selectivity can provide a promising alternative for H2O2 monitoring in vivo in the fields of physiology, pathology and diagnosis.

CT diagnosis of abdominal ectopic pheochromocytoma

International Nuclear Information System (INIS)

Zhang Yuping; Zhao Zhiying

2010-01-01

Objective: To discuss the value of CT in diagnosis of abdominal ectopic pheochromocytoma. Methods: CT findings of 5 cases surgically and pathologically proved with ectopic pheochromocytoma were retrospectively analyzed. Results: Soft tissue mass with light asymmetry enhancement was found between the abdominal aorta and the inferior vena ca-va in one case. 1 case was completely cystic with light enhancement of the cystwall located in front of the left side of the abdominal aorta. 1 case of large solid mass occurred between the renal hilum and the tail of pancreas, with irregular shape, unclear boundary, central necrosis, calcification and obviously enhancement at the solid part. 2 cases showed as oval soft lump with even density, moderate strengthening located before the abdominal aorta. Paroxysmal hypertension occurred in 3 cases and didn't in 2 cases. Hypertension happened in 1 case during the operation because of stimulation. Blood pressure appeared in 1 case during and after operation. Blood and urinary catecholamine increased significantly in 4 cases. Conclusion: Ectopic pheochromocytoma mainly located surround the abdominal aorta with diverse CT performance. It is helpful for diagnosing when finding a lesion locates at the specified sites combined with typical clinical presentation. CT can not only depict small tumor, but also can show the relationship with surrounding structure, and it provides important information for the operation and prognosis. (authors)

MANAGEMENT OF ENDOCRINE DISEASE: Outcome of adrenal sparing surgery in heritable pheochromocytoma.

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Castinetti, F; Taieb, D; Henry, J F; Walz, M; Guerin, C; Brue, T; Conte-Devolx, B; Neumann, H P H; Sebag, F

2016-01-01

The management of hereditary pheochromocytoma has drastically evolved in the last 20 years. Bilateral pheochromocytoma does not increase mortality in MEN2 or von Hippel-Lindau (VHL) mutation carriers who are followed regularly, but these mutations induce major morbidities if total bilateral adrenalectomy is performed. Cortical sparing adrenal surgery may be proposed to avoid definitive adrenal insufficiency. The surgical goal is to leave sufficient cortical tissue to avoid glucocorticoid replacement therapy. This approach was achieved by the progressive experience of minimally invasive surgery via the transperitoneal or retroperitoneal route. Cortical sparing adrenal surgery exhibits management of all patients with MEN2 or VHL hereditary pheochromocytoma. Hereditary pheochromocytoma is a rare disease, and a randomized trial comparing cortical sparing vs classical adrenalectomy is probably not possible. This lack of data most likely explains why cortical sparing surgery has not been adopted in most expert centers that perform at least 20 procedures per year for the treatment of this disease. This review examined recent data to provide insight into the technique, its indications, and the results and subsequent follow-up in the management of patients with hereditary pheochromocytoma with a special emphasis on MEN2. © 2016 European Society of Endocrinology.

Multiple adrenal masses: MRI tissue differentiation of pheochromocytoma and adenoma at 1.5 T

International Nuclear Information System (INIS)

Slapa, R.Z.; Jakubowski, W.; Feltynowski, T.; Januszewicz, A.

1997-01-01

We present the case of 38-year-old hypertensive patient with bilateral adrenal masses and with clinical and biochemical suspicion of pheochromocytoma. Magnetic resonance imaging at 1.5 T established correct diagnosis of coexisting adrenal pheochromocytoma and adenoma (nonhyperfunctioning). The case supports the usefulness of MRI for definitive evaluation of bilateral adrenal masses in patients with suspicion of pheochromocytoma. (orig.). With 2 figs

Pheochromocytoma as a frequent false-positive in adrenal washout CT. A systematic review and meta-analysis

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Woo, Sungmin; Kim, Sang Youn [Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Suh, Chong Hyun [University of Ulsan College of Medicine, Asan Medical Center, Department of Radiology and Research Institute of Radiology, Seoul (Korea, Republic of); Namwon Medical Center, Department of Radiology, Namwon-si, Jeollabuk-do (Korea, Republic of); Cho, Jeong Yeon; Kim, Seung Hyup [Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Seoul National University Medical Research Center, Institute of Radiation Medicine and Kidney Research Institute, Seoul (Korea, Republic of)

2018-03-15

To evaluate the proportion of pheochromocytomas meeting the criteria for adenoma on adrenal washout CT and the diagnostic performance of adrenal washout CT for differentiating adenoma from pheochromocytoma. MEDLINE and EMBASE were searched to 28 March 2017. We included studies that used adrenal washout CT for characterisation of pheochromocytomas. Two independent reviewers assessed the methodological quality using Quality Assessment of Diagnostic Accuracy Studies-2. Proportions were pooled using an inverse variance method for calculating weights (random-effects). Sensitivity and specificity were pooled using hierarchical logistic regression modelling and plotted in a hierarchical summary receiver-operating-characteristics (HSROC) plot. Ten studies (114 pheochromocytomas) were included. The pooled proportion of pheochromocytomas meeting the criteria for adenomas was 35 % (95 % CI 20-51). For eight studies providing information on diagnostic performance, the pooled sensitivity and specificity for differentiating adenoma from pheochromocytoma were 0.97 (95 % CI 0.93-0.99) and 0.67 (95 % CI 0.44-0.84), respectively. The area under the HSROC curve was 0.97 (95 % CI 0.95-0.98). There was a non-negligible proportion of pheochromocytomas meeting the criteria for adenoma on adrenal washout CT. Although overall diagnostic performance was excellent for differentiating adenoma from pheochromocytoma, specificity was relatively low. (orig.)

Pheochromocytoma as a frequent false-positive in adrenal washout CT. A systematic review and meta-analysis

International Nuclear Information System (INIS)

Woo, Sungmin; Kim, Sang Youn; Suh, Chong Hyun; Cho, Jeong Yeon; Kim, Seung Hyup

2018-01-01

To evaluate the proportion of pheochromocytomas meeting the criteria for adenoma on adrenal washout CT and the diagnostic performance of adrenal washout CT for differentiating adenoma from pheochromocytoma. MEDLINE and EMBASE were searched to 28 March 2017. We included studies that used adrenal washout CT for characterisation of pheochromocytomas. Two independent reviewers assessed the methodological quality using Quality Assessment of Diagnostic Accuracy Studies-2. Proportions were pooled using an inverse variance method for calculating weights (random-effects). Sensitivity and specificity were pooled using hierarchical logistic regression modelling and plotted in a hierarchical summary receiver-operating-characteristics (HSROC) plot. Ten studies (114 pheochromocytomas) were included. The pooled proportion of pheochromocytomas meeting the criteria for adenomas was 35 % (95 % CI 20-51). For eight studies providing information on diagnostic performance, the pooled sensitivity and specificity for differentiating adenoma from pheochromocytoma were 0.97 (95 % CI 0.93-0.99) and 0.67 (95 % CI 0.44-0.84), respectively. The area under the HSROC curve was 0.97 (95 % CI 0.95-0.98). There was a non-negligible proportion of pheochromocytomas meeting the criteria for adenoma on adrenal washout CT. Although overall diagnostic performance was excellent for differentiating adenoma from pheochromocytoma, specificity was relatively low. (orig.)

Treatment Option Overview (Pheochromocytoma and Paraganglioma)

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... foods high in tyramine (such as red wine, chocolate, and cheese). Tests that examine the blood and ... cause signs or symptoms are treated with drug therapy. Drug therapy begins when pheochromocytoma or paraganglioma is ...

General Information about Pheochromocytoma and Paraganglioma

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... foods high in tyramine (such as red wine, chocolate, and cheese). Tests that examine the blood and ... cause signs or symptoms are treated with drug therapy. Drug therapy begins when pheochromocytoma or paraganglioma is ...

Treatment Options for Pheochromocytoma and Paraganglioma

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... foods high in tyramine (such as red wine, chocolate, and cheese). Tests that examine the blood and ... cause signs or symptoms are treated with drug therapy. Drug therapy begins when pheochromocytoma or paraganglioma is ...

Differentiating pheochromocytoma from lipid-poor adrenocortical adenoma by CT texture analysis: feasibility study.

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Zhang, Gu-Mu-Yang; Shi, Bing; Sun, Hao; Jin, Zheng-Yu; Xue, Hua-Dan

2017-09-01

To investigate the feasibility of using CT texture analysis (CTTA) to differentiate pheochromocytoma from lipid-poor adrenocortical adenoma (lp-ACA). Ninety-eight pheochromocytomas and 66 lp-ACAs were included in this retrospective study. CTTA was performed on unenhanced and enhanced images. Receiver operating characteristic (ROC) analysis was performed, and the area under the ROC curve (AUC) was calculated for texture parameters that were significantly different for the objective. Diagnostic accuracies were evaluated using the cutoff values of texture parameters with the highest AUCs. Compared to lp-ACAs, pheochromocytomas had significantly higher mean gray-level intensity (Mean), entropy, and mean of positive pixels (MPP), but lower skewness and kurtosis on unenhanced images (P feasible to use CTTA to differentiate pheochromocytoma from lp-ACA.

MR imaging of an intrapericardial pheochromocytoma

International Nuclear Information System (INIS)

Fisher, M.R.; Higgins, C.B.; Andereck, W.

1985-01-01

The magnetic resonance (MR) appearance of an intrapericardial pheochromocytoma is reported, and the role of MR, compared with CT and a 131 I-metaiodobenzylguanidine scan in delineating masses from cardiac and vascular structures in the mediastinum is discussed

Is the excess cardiovascular morbidity in pheochromocytoma related to blood pressure or to catecholamines?

Science.gov (United States)

Stolk, Roeland F; Bakx, Carel; Mulder, Jan; Timmers, Henri J L M; Lenders, Jacques W M

2013-03-01

It is generally accepted that pheochromocytoma is associated with an increased cardiovascular risk. This is however not based on studies with an appropriate control group of patients with essential hypertension. We examined whether patients with pheochromocytoma have an excess cardiovascular morbidity as compared to hypertensive patients. In a retrospective case-control study we reviewed the medical charts of 109 pheochromocytoma patients for cardiovascular events within 5 years prior to the diagnosis. These patients were matched to control patients with essential hypertension for gender and year of birth and diagnosis. Outcome variables were ischemic heart disease, cerebrovascular accidents, and transient ischemic attacks. Classical cardiovascular risk factors were also assessed. A significantly higher rate of patients with pheochromocytoma suffered a cardiovascular event (13.8%; 95% confidence interval: 7.9%-21.6%) as compared to hypertensive patients (1.1%, 95% confidence interval: 0.1%-3.9%) (P risk factors. Pheochromocytoma patients have a clearly higher rate of cardiovascular events than patients with essential hypertension. This cannot be attributed to differences in blood pressure or other cardiovascular risk factors. The most likely explanation for the excess event rate is the prolonged exposure to the toxic effects of tumoral catecholamines. These data underpin the importance of a timely diagnosis and treatment of pheochromocytoma.

A Clinical Roadmap to Investigate the Genetic Basis of Pediatric Pheochromocytoma: Which Genes Should Physicians Think About?

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Bernardo Dias Pereira

2018-01-01

Full Text Available Pheochromocytoma is very rare at a pediatric age, and when it is present, the probability of a causative genetic mutation is high. Due to high costs of genetic surveys and an increasing number of genes associated with pheochromocytoma, a sequential genetic analysis driven by clinical and biochemical phenotypes is advised. The published literature regarding the genetic landscape of pediatric pheochromocytoma is scarce, which may hinder the establishment of genotype-phenotype correlations and the selection of appropriate genetic testing at this population. In the present review, we focus on the clinical phenotypes of pediatric patients with pheochromocytoma in an attempt to contribute to an optimized genetic testing in this clinical context. We describe epidemiological data on the prevalence of pheochromocytoma susceptibility genes, including new genes that are expanding the genetic etiology of this neuroendocrine tumor in pediatric patients. The clinical phenotypes associated with a higher pretest probability for hereditary pheochromocytoma are presented, focusing on differences between pediatric and adult patients. We also describe new syndromes, as well as rates of malignancy and multifocal disease associated with these syndromes and pheochromocytoma susceptibility genes published more recently. Finally, we discuss new tools for genetic screening of patients with pheochromocytoma, with an emphasis on its applicability in a pediatric population.

Hypertensive crisis in pregnancy due to a metamorphosing pheochromocytoma with postdelivery Cushing's syndrome.

Science.gov (United States)

Langton, Katharina; Gruber, Matthias; Masjkur, Jimmy; Steenblock, Charlotte; Peitzsch, Mirko; Meinel, Jörn; Lenders, Jacques; Bornstein, Stefan; Eisenhofer, Graeme

2018-01-01

Pheochromocytomas in pregnancy are rare but potentially lethal. Even rarer is the combination of pheochromocytoma in pregnancy with subsequent development of ectopic Cushing's syndrome. We report a 36-year-old woman, previously diagnosed with essential hypertension, who developed severe hypertension in pregnancy complicated by insulin-dependent gestational diabetes. A cesarean section was performed at 32 weeks following a hypertensive crisis after routine administration of betamethasone. Postnatal persistence of signs and symptoms of catecholamine excess led to the diagnosis of a left adrenal pheochromocytoma. Between diagnosis and planned tumor removal, the patient developed signs and symptoms of Cushing's syndrome (facial edema and hirsutism, myopathy and fatigue). Biochemical testing confirmed hypercortisolism with extremely elevated levels of plasma adrenocorticotropin, urinary cortisol and multiple steroids of a plasma panel that were all normal at previous testing. The previously noradrenergic tumor also started producing epinephrine. Histopathological examination confirmed the pheochromocytoma, which was also immunohistochemically positive for adrenocorticotropin. Full post-surgical recovery was sustained with normal blood pressure and biochemical findings after one year. This report not only underlines the chameleon behavior of pheochromocytoma but also illustrates its potential for a metamorphosing presentation. Corticosteroid administration in pregnancy requires a cautious approach in patients with hypertension.

Childhood familial pheochromocytoma. Conflicting results of localization techniques

International Nuclear Information System (INIS)

Turner, M.C.; DeQuattro, V.; Falk, R.; Ansari, A.; Lieberman, E.

1986-01-01

Childhood familial pheochromocytoma was investigated in four patients by abdominal computed tomographic scan, [ 131 I]metaiodobenzylguanidine scan, and vena caval catecholamine sampling. Results conflicted with surgical findings. Computed tomographic scan identified all four adrenal tumors but missed two midline tumors in one patient. [ 131 I]metaiodobenzylguanidine scan identified two of three adrenal tumors but also suggested extra-adrenal tumors not confirmed at operation in two of three patients. Vena caval sampling for catecholamines confirmed all adrenal tumors but suggested additional tumors not verified at operation in two of three patients. All patients are asymptomatic and have normal urinary catecholamines 15 to 51 months after operation. Because of the frequency of multiple tumors in familial pheochromocytoma, different diagnostic techniques were employed. False-positive results were more frequent with [ 131 I]metaiodobenzylguanidine and vena caval sampling. Reinterpretation of the [ 131 I]metaiodobenzylguanidine scans at a later date led to less false-positive interpretation, although the false-negative rate remained unchanged. More pediatric experience with [ 131 I]metaiodobenzylguanidine scans and vena caval sampling in familial pheochromocytoma is needed. Confirmation of tumor and its localization rest with meticulous surgical exploration

Reversible catecholamine-induced cardiomyopathy due to pheochromocytoma: case report.

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Satendra, Milan; de Jesus, Cláudia; Bordalo e Sá, Armando L; Rosário, Luís; Rocha, José; Bicha Castelo, Henrique; Correia, Maria José; Nunes Diogo, António

2014-03-01

Pheochromocytoma is a tumor originating from chromaffin tissue. It commonly presents with symptoms and signs of catecholamine excess, such as hypertension, tachycardia, headache and sweating. Cardiovascular manifestations include catecholamine-induced cardiomyopathy, which may present as severe left ventricular dysfunction and congestive heart failure. We report a case of pheochromocytoma which was diagnosed following investigation of dilated cardiomyopathy. We highlight the dramatic symptomatic improvement and reversal of cardiomyopathy, with recovery of left ventricular function after treatment. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Rapid reversal of heart failure in a patient with pheochromocytoma and catecholamine-induced myocarditis/cardiomyopathy

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Ahmed, I.; Sankaran, R.; Al-Addad, A.

2002-01-01

Pheochromocytoma is rare and usually presents as paroxysal or sustained hypertension, nonetheless, it can also cause severe acute pulmonary edema in normotensive individuals. We present a case with pheochromocytoma and severe left ventricular failure caused by catecholamine induced myocarditis/cardiomyopathy. Severe left ventricular failure resolved rapidly and left ventricular systolic function became normal within two weeks of medical treatment. Later, patient underwent elective and uneventful surgical removal of pheochromocytoma. (author)

[Pheochromocytoma in 8-year observation at a single endocrinological center in Wroclaw].

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Bednarek-Tupikowska, Grazyna; Bucyk, Barbara; Daroszewski, Jacek; Bidzińska-Speichert, Bozena; Bohdanowicz-Pawlak, Anna; Szymczak, Jadwiga; Bednorz, Włodzimierz; Podgórski, Franciszek; Zareba-Bogdał, Elzbieta; Kuliczkowska-Płaksej, Justyna; Lenarcik, Agnieszka; Filus, Alicja; Kałuzny, Marcin; Kubicka, Eliza; Syrycka, Joanna; Tupikowska, Małgorzata; Lizurej, Oskar; Bolanowski, Marek; Milewicz, Andrzej

2009-01-01

Pheochromocytoma is rare tumor with a highly variable clinical presentation. This report provides clinical picture, efficiency of diagnostics and treatment of pheochromocytoma in 8-years in the endocrinological center in Wroclaw. The records of 37 patients with pheochromocytoma were identified, who were treated in 2000-2007 in the Department of Endocrinology, Diabetology and Isotope Treatment in Wroclaw. There were 23 women (age 23-75 year) and 14 men (age 17-74). We studied frequency of clinical signs, usefulness of diagnostic methods and efficacy of treatment. The duration of the clinical history ranged from 2 months to 16 years. The most frequent symptoms were: hypertension paroxysmal and constant, palpitations, headache, sweating and anxiety. The most sensitive diagnostic method was increased concentration of urinary metanephrine in 24-hour urine. Computed tomography was the most widely used method for tumor localization. Adrenal pheochromocytoma was detecting by CT in all patients, predominated in right adrenal, in 1 case in urinary bladder. Surgery caused remission of hypertension in 59%, improvement in 26.8%, and no changes in 13.9% of patients. Malignancy was reported in 2 cases, 1 woman died after surgery. MEN 2A occur in 21.6%. The diagnosis of pheochromocytma is usually made after long duration of the disease. The study confirms that clinical presentation of pheochromocytoma is variable and nonspecific, this finding makes the diagnosis very difficult. The most typical symptom is paroxysmal hypertension, which is present only in 40%, other symptoms are nonspecific. The measurement of 24-hour urinary metanephrines was the best indicator. CT was almost always successful in localizing the tumor. Patients with pheochromocytoma should be consider for other endocrine diseases especially medullary carcinoma, primary hyperparathyroidism and other component of MEN 2A.

Extra-adrenal pheochromocytoma in pregnancy: ultrasonography and magnetic resonance imaging findings

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Carson, B.J.W.; Johnston, M.A.; Iwaniuk, G.

1995-04-01

The case of a 24-year-old woman with extra-adrenal pheochromocytoma during pregnancy was described. Initial ultrasonography (US) at 27 weeks gestational age failed to show the pheochromocytoma, which was subsequently found by US at 35 weeks gestational age. Magnetic resonance imaging (MRI) provided diagnostic confirmation, as well as important information used by the obstetrician and the surgeon in operative planning. MRI proved to be ideally suited to investigation of extra-adrenal pheochromocytomas in pregnancy because it does not use ionizing radiation, and it has multiplanar capability and high contrast resolution. In the case described, the lesion was demonstrated with all MRI pulse sequences, but was best visualized with turbo spin-echo T2-weighted imaging, as well as with fat-suppressed imaging. 7 refs., 2 figs.

Pheochromocytoma and pregnancy: a deceptive connection.

NARCIS (Netherlands)

Lenders, J.W.M.

2012-01-01

A pheochromocytoma in a pregnant patient is one of the most threatening medical conditions for mother, fetus, and physician. Although extraordinarily rare with a frequency of 0.002% of all pregnancies, this tumor is notorious for its devastating consequences. As in non-pregnant patients, the signs

Adrenergic crisis due to pheochromocytoma - practical aspects. A short review.

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Juszczak, Kajetan; Drewa, Tomasz

2014-01-01

The definitive therapy in case of pheochromocytoma is complete surgical resection. Improper preoperative assessment and medical management generally places the patient at risk for complications, resulting from an adrenergic crisis. Therefore, it is crucial to adequately optimize these patients before surgery. Optimal preoperative medical management significantly decreases morbidity and mortality during the tumor resection. This review addresses current knowledge in pre- and intraoperative assessment of a patient with pheochromocytoma. Before surgery the patient is conventionally prepared with α-adrenergic blockade (over 10-14 days) and subsequently, additional β-adrenergic blockade is required to treat any associated tachyarrhythmias. In preoperative assessment, it is obligatory to monitor arterial blood pressure, heart rate, and arrhythmias and to restore the blood volume to normal. In conclusion, due to the pathophysiological complexity of a pheochromocytoma, the strict cooperation between the cardiologist, endocrinologist, surgeon and the anaesthesiologist for an uneventful outcome should be achieved in patients qualified for the surgical removal of such a tumor.

Acute aortic dissection in patient with suspected pheochromocytoma

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Lešanović Jelena

2016-01-01

Full Text Available Introduction: Aortic dissection is one of the most fatal vascular emergencies. Almost 40% of the patients do not reach hospital in time while more than quarter die in the first 24 hours after the dissection begins. Case Report: A 37-year old man was admitted to our hospital with severe anterior chest pain which had lasted for over a week. Suspected aortic dissection was rapidly confirmed using imaging modalities - MDCT chest scan and TTE, followed by an urgent surgical management - Bentall procedure. MDCT chest scan also discovered adrenal incidentaloma defined as malignant, pheochromocytoma like mass. Due to the critical state of the patient, there was not enough time for further endocrinologic testing. Discussion and conclusion: When treating patients with pheochromocytoma and acute aortic disection, it is crucial to obtain a stable hemodynamic state before the surgery, since they can trigger a severe hypertensive crisis due to high levels of cathecholamines induced chronic vasoconctriction. The most vulnerable periods are the induction of anesthesia and perioperative hemodynamic oscillations, so treating patients with short acting alpha- 1 adrenergic blocking agents preoperatively has proven to be helpful - Phentolamine. Both dissection of aorta and pheochromocytoma present challenges for anesthesiologists and early recognition of symptoms is essential in establishing the diagnosis and reducing the mortality rate.

Severe polyuria after the resection of adrenal pheochromocytoma.

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Tobe, Musashi; Ito, Keiichi; Umeda, Shun; Sato, Akinori; Adaniya, Noriaki; Tanaka, Yuji; Hayakawa, Masamichi; Asano, Tomohiko

2010-12-01

A 73-year-old male patient with hypertension and hyperglycemia was referred to our hospital because of a diagnosis regarding his left adrenal tumor. Because the levels of urinary metanephrine and normetanephrine were elevated, and (131) I-MIBG scintigraphy showed intense uptake in the adrenal tumor, the tumor was diagnosed as a pheochromocytoma. An adrenalectomy was carried out. Severe polyuria, which was accompanied by a rapid decrease in central venous pressure, started 1 hour after the operation. Urine output of more than 8000 mL/day continued until the 16th postoperative day. Plasma antidiuretic hormone (ADH) levels were within the normal range. Plasma human atrial natriuretic peptide (hANP) and brain natriuretic peptide (BNP) were elevated postoperatively, and the elevation of these peptides was one possible cause for the severe polyuria. Because ADH levels in the tumor fluid were not elevated, the tumor was not an ADH-secreting tumor. Urinary β2-microglobulin was significantly elevated after the operation, thus suggesting that renal tubule dysfunction might also have been involved in the polyuria. However, the mechanism of polyuria after the resection of adrenal pheochromocytoma is not fully understood. Polyuria after the resection of adrenal pheochromocytoma is extremely rare, and the present subject is the second case to date. © 2010 The Japanese Urological Association.

The importance of pheochromocytoma case detection in patients with neurofibromatosis type 1: A case report and review of literature.

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Tate, Joshua M; Gyorffy, Janelle B; Colburn, Jeffrey A

2017-01-01

Neurofibromatosis type 1 is a complex, multi-system genetic disorder that is associated with an increased prevalence of pheochromocytoma and paraganglioma compared to the general population, 1.0%-5.7% versus 0.2%-0.6%, respectively. A delay in pheochromocytoma and paraganglioma diagnosis or undiagnosed pheochromocytoma and paraganglioma, as seen in normotensive and asymptomatic patients, may portend a significant morbidity and mortality risk due to excess catecholamine secretion. Currently, there are no generally accepted guidelines of screening for pheochromocytoma and paragangliomas in asymptomatic individuals of this population with approaches and practices varying considerably between physicians. Emerging data suggest benefit in routine pheochromocytoma and paraganglioma screening of all individuals with neurofibromatosis type 1. Herein, we present a case to highlight how routine case detection screening would have identified pheochromocytoma earlier in an active duty military member.

Stroke and myocardial ischemia in a patient of pheochromocytoma: A rare clinical sequele

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Vivek Aggarwal

2006-01-01

Full Text Available Pheochromocytoma classically presents with paroxysms of hypertension and adrenergic symptoms including headaches, palpitation, tremor and anxiety. However, these tumors can be clinically silent and occasionally manifest only when catecholamine release is upregulated by exogenous stimuli. In addition, the clinical presentation of pheochromocytoma can mimic a number of other medical conditions including migraine, cardiac arrhythmias, myocardial infarction and stroke, thus, making the diagnosis of pheochromocytoma difficult. We present a case of a 43-year old male patient who presented for evaluation of adrenal mass in the department of endocrine surgery. This patient had a previous history of right side hemiperasis and lateral wall ischemia, with no residual clinical deficit.

Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma

NARCIS (Netherlands)

Fishbein, Lauren; Leshchiner, Ignaty; Walter, Vonn; Danilova, Ludmila; Robertson, A. Gordon; Johnson, Amy R.; Lichtenberg, Tara M.; Murray, Bradley A.; Ghayee, Hans K.; Else, Tobias; Ling, Shiyun; Jefferys, Stuart R.; de Cubas, Aguirre A.; Wenz, Brandon; Korpershoek, Esther; Amelio, Antonio L.; Makowski, Liza; Rathmell, W. Kimryn; Gimenez-Roqueplo, Anne Paule; Giordano, Thomas J.; Asa, Sylvia L.; Tischler, Arthur S.; Akbani, Rehan; Ally, Adrian; Amar, Laurence; Amelio, Antonio L.; Arachchi, Harindra; Asa, Sylvia L.; Auchus, Richard J.; Auman, J. Todd; Baertsch, Robert; Balasundaram, Miruna; Balu, Saianand; Bartsch, Detlef K.; Baudin, Eric; Bauer, Thomas; Beaver, Allison; Benz, Christopher; Beroukhim, Rameen; Beuschlein, Felix; Bodenheimer, Tom; Boice, Lori; Bowen, Jay; Bowlby, Reanne; Brooks, Denise; Carlsen, Rebecca; Carter, Suzie; Cassol, Clarissa A.; Cherniack, Andrew D.; Chin, Lynda; Cho, Juok; Chuah, Eric; Chudamani, Sudha; Cope, Leslie; Crain, Daniel; Curley, Erin; Danilova, Ludmila; de Cubas, Aguirre A.; de Krijger, Ronald R.; Demchok, John A.; Deutschbein, Timo; Dhalla, Noreen; Dimmock, David; Dinjens, Winand N M; Else, Tobias; Eng, Charis; Eschbacher, Jennifer; Fassnacht, Martin; Felau, Ina; Feldman, Michael; Ferguson, Martin L.; Fiddes, Ian; Fishbein, Lauren; Frazer, Scott; Gabriel, Stacey B.; Gardner, Johanna; Gastier-Foster, Julie M.; Gehlenborg, Nils; Gerken, Mark; Getz, Gad; Geurts, Jennifer; Ghayee, Hans K.; Gimenez-Roqueplo, Anne Paule; Giordano, Thomas J.; Goldman, Mary; Graim, Kiley; Gupta, Manaswi; Haan, David; Hahner, Stefanie; Hantel, Constanze; Haussler, David; Hayes, D. Neil; Heiman, David I.; Hoadley, Katherine A.; Holt, Robert A.; Hoyle, Alan P.; Huang, Mei; Hunt, Bryan; Hutter, Carolyn M.; Jefferys, Stuart R.; Johnson, Amy R.; Jones, Steven J M; Jones, Corbin D.; Kasaian, Katayoon; Kebebew, Electron; Kim, Jaegil; Kimes, Patrick; Knijnenburg, Theo; Korpershoek, Esther; Lander, Eric; Lawrence, Michael S.; Lechan, Ronald; Lee, Darlene; Leraas, Kristen M.; Lerario, Antonio; Leshchiner, Ignaty; Lichtenberg, Tara M.; Lin, Pei; Ling, Shiyun; Liu, Jia; LiVolsi, Virginia A.; Lolla, Laxmi; Lotan, Yair; Lu, Yiling; Ma, Yussanne; Maison, Nicole; Makowski, Liza; Mallery, David; Mannelli, Massimo; Marquard, Jessica; Marra, Marco A.; Matthew, Thomas; Mayo, Michael; Méatchi, Tchao; Meng, Shaowu; Merino, Maria J.; Mete, Ozgur; Meyerson, Matthew; Mieczkowski, Piotr A.; Mills, Gordon B.; Moore, Richard A.; Morozova, Olena; Morris, Scott; Mose, Lisle E.; Mungall, Andrew J.; Murray, Bradley A.; Naresh, Rashi; Nathanson, Katherine L.; Newton, Yulia; Ng, Sam; Ni, Ying; Noble, Michael S.; Nwariaku, Fiemu; Pacak, Karel; Parker, Joel S.; Paul, Evan; Penny, Robert; Perou, Charles M.; Perou, Amy H.; Pihl, Todd; Powers, James; Rabaglia, Jennifer; Radenbaugh, Amie; Ramirez, Nilsa C.; Rao, Arjun; Rathmell, W. Kimryn; Riester, Anna; Roach, Jeffrey; Robertson, A. Gordon; Sadeghi, Sara; Saksena, Gordon; Salama, Sofie; Saller, Charles; Sandusky, George; Sbiera, Silviu; Schein, Jacqueline E.; Schumacher, Steven E.; Shelton, Candace; Shelton, Troy; Sheth, Margi; Shi, Yan; Shih, Juliann; Shmulevich, Ilya; Simons, Janae V.; Sipahimalani, Payal; Skelly, Tara; Sofia, Heidi J.; Sokolov, Artem; Soloway, Matthew G.; Sougnez, Carrie; Stuart, Josh; Sun, Charlie; Swatloski, Teresa; Tam, Angela; Tan, Donghui; Tarnuzzer, Roy; Tarvin, Katherine; Thiessen, Nina; Thorne, Leigh B.; Timmers, Henri J.; Tischler, Arthur S.; Tse, Kane; Uzunangelov, Vlado; van Berkel, Anouk; Veluvolu, Umadevi; Vicha, Ales; Voet, Doug; Waldmann, Jens; Walter, Vonn; Wan, Yunhu; Wang, Zhining; Wang, Tracy S.; Weaver, Joellen; Weinstein, John N.; Weismann, Dirk; Wenz, Brandon; Wilkerson, Matthew D.; Wise, Lisa; Wong, Tina; Wong, Christopher; Wu, Ye; Yang, Liming; Zelinka, Tomas; Zenklusen, Jean C.; Zhang, Jiashan (Julia); Zhang, Wei; Zhu, Jingchun; Zinzindohoué, Franck; Zmuda, Erik; Pacak, Karel; Nathanson, Katherine L.; Wilkerson, Matthew D.

2017-01-01

We report a comprehensive molecular characterization of pheochromocytomas and paragangliomas (PCCs/PGLs), a rare tumor type. Multi-platform integration revealed that PCCs/PGLs are driven by diverse alterations affecting multiple genes and pathways. Pathogenic germline mutations occurred in eight

Pheochromocytoma of the urinary bladder - a case report

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Marić Predrag

2016-01-01

Full Text Available Introduction. Pheochromocytoma of the urinary bladder is a rare tumor and presents less than 0.06% of all urinary bladder tumors. Case report. We presented a 49-year-old female patient with a history of daily paroxysmal hypertension accompanied with flushing of the face and upper chest, palpitations and excessive sweating prior to micturition. Ultrasonography reported a 3 cm bladder wall tumor. The 131I-metaiodobenzylguanidine (131I-MIBG scan showed a pathological isotope accumulation in the projection of the bladder. The patient underwent a partial cystectomy. One year following the operation the patient was normotensive and without recurrence. Conclusion. The most efficient treatment option for bladder pheochromocytoma is surgical resection. The most important fact in the diagnostics is suspicion on this rare condition.

Pheochromocytomas and paragangliomas in humans and dogs

NARCIS (Netherlands)

Galac, S.; Korpershoek, E

2017-01-01

Pheochromocytomas (PCCs) and paragangliomas (PGLs) are described in several species. In humans and dogs they have many similarities: the excessive catecholamine release in hormonally active PCC causes similar clinical signs, the frequency of metastasis is similar, and they are histopathologically

Implications and considerations during pheochromocytoma resection: A challenge to the anesthesiologist

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Sukhminder Jit Singh Bajwa

2011-01-01

Full Text Available Pheochromocytoma is a rare catecholamine secreting tumor arising commonly from adrenal medulla. It has got multidimensional challenging aspects in spite of our improved understanding of its physiological and clinical behavior during surgical resection. This neuroendocrine tumor is associated with a most unpredictable and fluctuating clinical course during anesthesia and surgical intervention. The clinical difficulties and challenges increase manifold in patients with undiagnosed or accidental diagnosis of pheochromocytoma who present to the hospital for the treatment of some other disease or emergency. The most common manifestations of this clinical spectrum include hypertension, headache, palpitations, episodic sweating, and feeling of doom. The definite and only treatment for this rare tumor is surgical resection which itself is very challenging for an anesthesiologist. This article reviews the pre-operative evaluation, pharmacological preparation, intraoperative and post-operative management of patients with pheochromocytoma especially from anesthesiologist′s perspectives.

Pheochromocytoma of the Organ Zuckerkandl.

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Lee, C; Chang, E; Gimenez, J; McCarron, R

2017-01-01

Pheochromocytomas (PCCs);, or intra-adrenal paragangliomas (PGLs);, are neuroendocrine tumors arising within the adrenal medulla. Extra-adrenal paragangliomas may arise in the sympathetic or parasympathetic paraganglia and more rarely in other organs. One of the most common extra-adrenal sites is in the organ of Zuckerkandl, a collection of chromaffin cells near the origin of the inferior mesenteric artery or near the aortic bifurcation. The following is a case of a patient with resistant hypertension secondary to an extra-adrenal paraganglioma in the organ of Zuckerkandl. The patient is a 43 year old man with a history of depression, type 2 diabetes mellitus, and hypertension who was sent to the emergency department by his primary care physician for severely elevated blood pressures. Patient also had diaphoresis, tachycardia, and a new, fine tremor of his left hand. Upon presentation, the patient's blood pressure was 260/120 mmHg with a heart rate of 140 beats per minute. Plasma fractionated metanephrines sent on admission revealed significantly elevated levels of total plasma metanephrines (2558 pg/mL);, free metanephrine (74 pg/ml); and free normetanephrine (2484pg/mL);. An I-123 metaiodobenzylguanidine (MIBG); scan showed abnormal uptake in the lower abdomen at the level of the aortic bifurcation. Patient was started on alpha-blockade, with subsequent addition of a beta-blocker prior to surgery. Patient underwent surgical removal of the tumor with pathology consistent with a paraganglioma. Pheochromocytomas and paragangliomas are responsible for approximately 0.5 percent of cases of secondary hypertension. Many different biochemical markers have been used to aid in the diagnosis of PCC/PGL including plasma catecholamines, plasma metanephrines, urine fractionated metanephrines, urine catecholamines, total metanephrines and vanillymandellic acid. Definitive management of a PCC and PGL involves surgical removal of the tumor. Finally, there should be a discussion

Anesthesia Management for Pheochromocytoma Removal in a 17-Year-Old Girl: Case Report

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Gulsen Keskin

2018-03-01

Full Text Available A rare tumor of the chromaffin tissue, pheochromocytoma is characterized by increased secretion of catecholamines. Pediatric cases represent only 5% of all pheochromocytomas. In this report, we presented anesthesia management of a 17-year-old girl who would undergo right suprarenal mass excision due to pheochromocytoma accompanied with familial Mediterranean fever (FMF. Preoperative blood pressure control was achieved with phenoxybenzamine. General anesthesia was established with thiopental, vecuronium, fentanyl, and sevoflurane. Sodium nitroprusside and phentolamine was used for perioperative blood pressure control. Tramadol and diclofenac were administered for postoperative pain. The patient was discharged after a good preoperative preparation and perioperative management with uneventful treatment period. [J Contemp Med 2018; 8(1.000: 70-73

Iodine-131 MIBG scintigraphy of the extremities in metastatic pheochromocytoma and neuroblastoma

International Nuclear Information System (INIS)

Shulkin, B.L.; Shen, S.W.; Sisson, J.C.; Shapiro, B.

1987-01-01

Iodine-131 MIBG scintigraphy may be used to determine the presence or absence of metastases to the appendicular skeleton in malignant pheochromocytoma and neuroblastoma. Normal bones show no uptake of [ 131 I]MIBG and the joints are seen as photon-deficient areas surrounded by background muscle activity. Discrete concentrations of radioactivity in bone are often seen in patients with malignant pheochromocytoma and neuroblastoma. Bone marrow involvement in neuroblastoma may be indicated by diffuse uptake of [ 131 I]MIBG or focal accumulation at the metaphyses. Uncommonly, bone involvement may not be displayed by the [ 131 I]MIBG images. Since conventional bone scanning agents may also fail to detect these tumors, skeletal scintigraphy with both [ 131 I]MIBG and [/sup 99m/Tc]MDP is necessary to reliably stage malignant pheochromocytoma and neuroblastoma

Local absolute alcohol ablation for the treatment of recurrent pheochromocytoma

International Nuclear Information System (INIS)

Shang Mingyi; Wang Peijun; Lu Ying; Ma Jun; Tang Junjun; Xi Qian; Huang Zongliang; Gao Xiaolong

2010-01-01

Objective: to assess the clinical value of local injection of absolute alcohol under CT guidance in treating recurrent pheochromocytoma. Methods: Five patients with benign recurrent pheochromocytoma were enrolled in this study. Of the five cases, the lesions were located on the right side in three, on the left in one and on both sides in one. All the lesions were pathologically proved to be benign ones. Under CT guidance the ablation therapy with local injection of absolute alcohol was performed. The therapeutic results were observed and evaluated. Results: Thirty days after the treatment, different degrees of decrease in tumor size was observed on follow-up CT scans. All the patients were followed up for 9-42 months. During the follow-up period, both the blood pressure and the vanillyl mandelic acid (VMA) level in urine remained normal and no paroxysmal dizziness, headache or syncope occurred in all patients. Conclusion: For the treatment of recurrent pheochromocytoma the ablation therapy by using local injection of absolute alcohol under CT guidance is a safe and practical therapeutic means with definite and reliable effectiveness. (authors)

Adrenal incidentaloma: A case of pheochromocytoma with sub-clinical Cushing′s syndrome

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Ashutosh Goyal

2013-01-01

Full Text Available Adrenal incidentalomas (AIs are a cluster of different pathologies, but AIs with dual functional aspects are very rare. We report a case of AI with the evidence of both pheochromocytoma and sub-clinical Cushing′s syndrome. A 42-year-old female patient presented with the history of abdominal pain. Abdominal computed tomography revealed right adrenal mass suggestive of pheochromocytoma. On endocrine evaluation, she admitted history of intermittent headache and palpitations for 4 years and was on treatment for hypertension and diabetes. There were no signs and symptoms suggestive of Cushing′s syndrome. The laboratory data demonstrated 10 times raised 24-h urinary fractionated metanephrines with non-suppressible serum cortisol after 2-day low-dose dexamethasone suppression test. She underwent right-sided adrenalectomy with subsequent resolution of both pheochromocytoma and hypercortisolism. Patient was discharged in good clinical condition.

Scintigraphic localization of pheochromocytomas using 131 I-meta-iodobenzylguanidine. Comparison with computerized tomography

International Nuclear Information System (INIS)

Charbonnel, B.; Coornaert, S.; Tellier, J.L.; Peltier, P.; Chatal, J.F.

1984-01-01

Meta-iodobenzylguanidine was synthesized, radiolabelled with I 131 or I 123 and injected to 28 controls and 7 patients totalizing 13 foci of pheochromocytoma. The tumour was located in one adrenal gland in 3 cases, in both adrenal glands in 1 case, and between the aorta and the vena cava in 1 case; 2 were malignant with metastases. Scintigraphy was negative in all controls, whereas all pheochromocytomas were clearly demonstrated 24 h after injection, except one regarded as non functional due to necrosis. By comparison, CT readily showed the tumour in 7 cases, showed it only thanks to scintigraphic guidance in 4 cases and failed in 2 cases. It is concluded that scintigraphy with meta-iodo-benzylguanidine provides a safe and reliable means of locating a wide range of pheochromocytomas [fr

Two-stage resection of a bilateral pheochromocytoma and pancreatic neuroendocrine tumor in a patient with von Hippel-Lindau disease: A case report

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Yutaka Endo

Full Text Available Introduction: von Hippel-Lindau disease (vHL disease is a hereditary disease in which tumors and cysts develop in many organs, in association with central nervous system hemangioblastomas, pheochromocytomas, and pancreatic tumors. We herein report a case of vHL disease (type 2A associated with bilateral pheochromocytomas, pancreatic neuroendocrine tumors (PNET, and cerebellar hemangioblastomas treated via pancreatectomy after adrenalectomy. Case presentation: A 51-year-old woman presented with a cerebellar tumor, bilateral hypernephroma, and pancreatic tumor detected during a medical checkup. 18F-fluorodeoxyglucose positron emission tomography–computed tomography revealed a bilateral adrenal gland tumor and a tumor in the head of the pancreas, while an abdominal computed tomography examination revealed a 30-mm tumor with strong enhancement in the head of the pancreas. Cranial magnetic resonance imaging showed a hemangioblastoma in the cerebellum. Therefore, a diagnosis of vHL disease (type 2A was made. Her family medical history included renal cell carcinoma in her father and bilateral adrenal pheochromocytoma and spinal hemangioblastoma in her brother. A detailed examination of endocrine function showed that the adrenal mass was capable of producing catecholamine. Treatment of the pheochromocytoma was prioritized, and therefore, laparoscopic left adrenalectomy and subtotal resection of the right adrenal gland were performed. Once the postoperative steroid levels were replenished, subtotal stomach-preserving pancreatoduodenectomy was performed for the PNET. After a good postoperative course, the patient was discharged in remission on the 11th day following surgery. Histopathological examination findings indicated NET G2 (MIB-1 index 10–15% pT3N0M0 Stage II A and microcystic serous cystadenoma throughout the resected specimen. The patient is scheduled to undergo treatment for the cerebellar hemangioblastoma. Conclusion: A two-staged resection

Clevidipine for hypertension treatment in pheochromocytoma surgery.

Science.gov (United States)

Luis-García, C; Arbonés-Aran, E; Teixell-Aleu, C; Lorente-Poch, L; Trillo-Urrutia, L

2018-04-01

Pheochromocytoma is a catecholamine-producing tumour and laparoscopic adrenalectomy is its treatment of choice. During pneumoperitoneum insufflation and tumour handling there is a high risk of massive catecholamine release and hypertensive crisis. After tumour excision, severe arterial hypotension is a common effect, due to relative vasodilation and the residual effect of antihypertensive drugs. We report the case of a patient with pheochromocytoma who was treated with laparoscopic adrenalectomy. During surgical manipulation there was a sudden hypertensive peak that could be controlled quickly with clevidipine infusion. After tumour resection, clevidipine perfusion was stopped and there were no arterial hypotension episodes. Clevidipine is a new intravenous calcium antagonist with rapid onset of action and short half-life that has no residual effect and does not produce arterial hypotension after tumour resection. For these reasons, it can be a first-choice drug for this kind of surgery. Copyright © 2017 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

A diagnosis pitfall: the cystic bilateral pheochromocytoma. Discussion of a case

International Nuclear Information System (INIS)

Devillers, A.; Bedig, G.; Garin, E.; Bouyaux, M.; Lecloirec, J.

1997-01-01

We report here the clinical history of Mrs A. (37 years old). On November 1995 Mrs A. presents stereotypical paroxysmal (2 to 3 / month) strokes of type of sensation of fast palpitations followed by very intense cephalies and sweats. The hypothesis of a pheochromocytoma has been retained, confirmed by a very important increase in the urinary metanephrines and normetanephrines and of noradrenaline. The abdominal scanner evidenced a left supra-renal tumoral lesion and also a voluminous right-renal cyst overflowing the right supra-renal. In May 1996 Mrs A. benefited by a left supra-renal-ectomy which confirmed histologically a benign pheochromocytoma. Long after the intervention the patient is totally asymptomatic but the metanephrines remains high (3000 μ g/24 h). The scanner applied in December 1996 finds only the voluminous right-renal cyst formation which perturbs the supra-renal exploration and rises questions about relic thymus. A scintigraphy by MIBG- 131 I evidenced on the images after 24 h a hyper-fixation with hepatic projections seeming to circumscribe a voluminous right-supra-renal lacuna, confirmed by injection of 20 mCi of pertechnetate, while at 48 h this image reinforces. The diagnosis of a cystized left pheochromocytoma was established while the thymus region was normal. A scintigraphy with somatostatin labelled by indium 111 finds the anomalies superimposed on those obtained by MIBG. The patient was operated in May 1997 and a diagnosis was histologically confirmed. In conclusion, the scintigraphy by MIBG 131 I must be part in the examination for suspicion of pheochromocytoma and must be interpreted together with the TDM morphological data

99mTc-HYNIC-TOC scintigraphy is superior to 131I-MIBG imaging in the evaluation of extraadrenal pheochromocytoma.

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Chen, Libo; Li, Fang; Zhuang, Hongming; Jing, Hongli; Du, Yanrong; Zeng, Zhengpei

2009-03-01

In this investigation, the efficacy of scintigraphy using (99m)Tc-labeled hydrazinonicotinyl-Tyr3-octreotide (HYNIC-TOC) in the evaluation of extraadrenal pheochromocytoma was assessed and compared with (131)I-labeled metaiodobenzylguanidine (MIBG) imaging. Ninety-seven patients who were suspected of having pheochromocytoma but showed no definite adrenal abnormalities on CT were evaluated by both (99m)Tc-HYNIC-TOC scintigraphy and (131)I-MIBG imaging. The results were compared with pathology findings or clinical follow-up. Of 58 patients proven to be without pheochromocytoma, (99m)Tc-HYNIC-TOC and (131)I-MIBG imaging excluded 56 and 58 patients, respectively, rendering a specificity of 96.6% for (99m)Tc-HYNIC-TOC imaging and 100% for (131)I-MIBG imaging. In the evaluation of adrenal pheochromocytoma (14 patients), the sensitivity of (99m)Tc-HYNIC-TOC scintigraphy and (131)I-MIBG imaging was 50% and 85.7%, respectively. However, in the evaluation of extraadrenal pheochromocytomas (25 patients), the sensitivity of (99m)Tc-HYNIC-TOC scintigraphy and (131)I-MIBG imaging was 96.0% and 72.0%, respectively. (99m)Tc-HYNIC-TOC scintigraphy is more sensitive than (131)I-MIBG imaging in the detection of extraadrenal pheochromocytomas.

[sup 131]I-metaiodobenzylguanidine therapy for malignant pheochromocytoma

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Sakahara, Harumi; Saga, Tsuneo; Hosono, Makoto; Kobayashi, Hisataka; Konishi, Junji (Kyoto Univ. (Japan). Faculty of Medicine); Endo, Keigo

1994-05-01

[sup 131]I-metaiodobenzylguanidine (MIBG) therapy was given to five patients with malignant pheochromocytoma. The patients received 1-3 doses of 3.33-4.625 GBq (total dose: 3.7 to 10.73 GBq). Partial tumor regression was observed in two patients, the tumor was unchanged in two patients, and slow progression was noted in one patient. Marked improvement in clinical symptoms was achieved in four patients. The other patients had no symptoms before [sup 131]I-MIBG treatment, but the serum epinephrine and dopamine decreased. There were no severe untoward responses in four patients. However, one patient developed transient but severe orthostatic hypotension, hypertension, and hyperglycemia from 1 week to 1 month after [sup 131]I-MIBG administration. Although complete remission was not obtained, all the patients achieved some benefit from [sup 131]I-MIBG therapy. Thus, [sup 131]I-MIBG appears to be useful for the palliation of malignant pheochromocytoma. (author).

Precision medicine in pheochromocytoma and paraganglioma: current and future concepts.

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Björklund, P; Pacak, K; Crona, J

2016-12-01

Pheochromocytoma and paraganglioma (PPGL) are rare diseases but are also amongst the most characterized tumour types. Hence, patients with PPGL have greatly benefited from precision medicine for more than two decades. According to current molecular biology and genetics-based taxonomy, PPGL can be divided into three different clusters characterized by: Krebs cycle reprogramming with oncometabolite accumulation or depletion (group 1a); activation of the (pseudo)hypoxia signalling pathway with increased tumour cell proliferation, invasiveness and migration (group 1b); and aberrant kinase signalling causing a pro-mitogenic and anti-apoptotic state (group 2). Categorization into these clusters is highly dependent on mutation subtypes. At least 12 different syndromes with distinct genetic causes, phenotypes and outcomes have been described. Genetic screening tests have a documented benefit, as different PPGL syndromes require specific approaches for optimal diagnosis and localization of various syndrome-related tumours. Genotype-tailored treatment options, follow-up and preventive care are being investigated. Future new developments in precision medicine for PPGL will mainly focus on further identification of driver mechanisms behind both disease initiation and malignant progression. Identification of novel druggable targets and prospective validation of treatment options are eagerly awaited. To achieve these goals, we predict that collaborative large-scale studies will be needed: Pheochromocytoma may provide an example for developing precision medicine in orphan diseases that could ultimately aid in similar efforts for other rare conditions. © 2016 The Association for the Publication of the Journal of Internal Medicine.

Adrenal and extra-adrenal pheochromocytomas presenting as life-threatening ventricular arrhythmias: Report of three cases

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Sai Satish Oruganti

2016-05-01

Full Text Available Pheochromocytoma patients can rarely have prolonged QT interval in the ECG. We report three cases of pheochromocytoma in females presenting with ventricular arrhythmia; two had torsades de pointes and a third patient had frequent VPCs and nonsustained ventricular tachycardia. All the patients were treated with surgical removal of the tumor with complete relief of symptoms and normalization of QT interval.

Thyrotoxic and pheochromocytoma multisystem crisis: a case report.

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Suzuki, Kodai; Miyake, Takahito; Okada, Hideshi; Yamaji, Fuminori; Kitagawa, Yuichiro; Fukuta, Tetsuya; Yasuda, Ryu; Tanaka, Yoshihito; Okamoto, Haruka; Nachi, Sho; Doi, Tomoaki; Yoshida, Takahiro; Kumada, Keisuke; Yoshida, Shozo; Ushikoshi, Hiroaki; Toyoda, Izumi; Ogura, Shinji

2017-06-23

Thyrotoxic crisis and pheochromocytoma multisystem crisis are rare, life-threatening, emergency endocrine diseases with various clinical manifestations. Here we report a case of a patient who simultaneously developed thyrotoxic crisis and pheochromocytoma multisystem crisis and required intensive cardiovascular management. A 60-year-old Asian man experienced nausea and vomiting, and subsequently developed dyspnea and cold sweats while farming. His serum free thyroxine, free triiodothyronine, and thyrotropin receptor antibody levels were elevated at 2.9 ng/dL, 7.2 pg/dL, and 4.7 IU/L, respectively. Serum thyrotropin levels were suppressed at less than 0.01 μIU/mL. Thyroid echography demonstrated no thyroid swelling (23 × 43 mm). A whole body computed tomography was performed for systemic evaluation. This revealed exophthalmos and a mass of size 57 × 64 mm in the anterior pararenal space. Based on these findings, we made an initial diagnosis of thyrotoxic crisis secondary to exacerbation of Grave's hyperthyroidism. Treatment was begun with an iodine agent at a dose of 36 mg/day, thiamazole at a dose of 30 mg/day, and hydrocortisone at a dose of 300 mg daily for 3 consecutive days. To control tachycardia, continuous intravenously administered propranolol and diltiazem infusions were given. At the same time, small doses of doxazosin and carvedilol were used for both alpha and beta adrenergic blockade. On hospital day 5, his blood pressure and serum catecholamine concentrations (adrenalin 42,365 pg/mL, dopamine 6409 pg/mL, noradrenalin 72,212 pg/mL) were still high despite higher beta blocker and calcium channel blocker doses. These findings contributed to the diagnosis of pheochromocytoma multisystem crisis with simultaneous thyrotoxic crisis. We increased the doses of doxazosin and carvedilol, which stabilized his hemodynamic status. On hospital day 16, metaiodobenzylguanidine scintigraphy showed high accumulation in the right adrenal gland tumor

Neurite outgrowth stimulatory effects of myco synthesized AuNPs from Hericium erinaceus (Bull.: Fr.) Pers. on pheochromocytoma (PC-12) cells.

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Raman, Jegadeesh; Lakshmanan, Hariprasath; John, Priscilla A; Zhijian, Chan; Periasamy, Vengadesh; David, Pamela; Naidu, Murali; Sabaratnam, Vikineswary

2015-01-01

Hericium erinaceus has been reported to have a wide range of medicinal properties such as stimulation of neurite outgrowth, promotion of functional recovery of axonotmetic peroneal nerve injury, antioxidant, antihypertensive, and antidiabetic properties. In recent years, the green synthesis of gold nanoparticles (AuNPs) has attracted intense interest due to the potential use in biomedical applications. The aim of this study was to investigate the effects of AuNPs from aqueous extract of H. erinaceus on neurite outgrowth of rat pheochromocytoma (PC-12) cells. The formation of AuNPs was characterized by UV-visible spectrum, energy dispersive X-ray (EDX), field-emission scanning electron microscope (FESEM), transmission electron microscopy (TEM), particle size distribution, and Fourier transform-infrared spectroscopy (FTIR). Furthermore, the neurite extension study of synthesized AuNPs was evaluated by in vitro assay. The AuNPs exhibited maximum absorbance between 510 and 600 nm in UV-visible spectrum. FESEM and TEM images showed the existence of nanoparticles with sizes of 20-40 nm. FTIR measurements were carried out to identify the possible biomolecules responsible for capping and efficient stabilization of the nanoparticles. The purity and the crystalline properties were confirmed by EDX diffraction analysis, which showed strong signals with energy peaks in the range of 2-2.4 keV, indicating the existence of gold atoms. The synthesized AuNPs showed significant neurite extension on PC-12 cells. Nerve growth factor 50 ng/mL was used as a positive control. Treatment with different concentrations (nanograms) of AuNPs resulted in neuronal differentiation and neuronal elongation. AuNPs induced maximum neurite outgrowth of 13% at 600 ng/mL concentration. In this study, the AuNPs synthesis was achieved by a simple, low-cost, and rapid bioreduction approach. AuNPs were shown to have potential neuronal differentiation and stimulated neurite outgrowth. The water

Carbon Fiber Ultramicrodic Electrode Electrodeposited with Over-Oxidized Polypyrrole for Amperometric Detection of Vesicular Exocytosis from Pheochromocytoma Cell

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Li Wang

2015-01-01

Full Text Available Vesicular exocytosis is ubiquitous, but it is difficult to detect within the cells’ communication mechanism. For this purpose, a 2 µm ultramicrodic carbon fiber electrode was fabricated in this work based on electrodeposition with over-oxidized polypyrrole nanoparticle (PPyox-CFE, which was applied successfully for real-time monitoring of quantal exocytosis from individual pheochromocytoma (PC12 cells. PPyox-CFE was evaluated by dopamine (DA solutions through cyclic voltammetry and amperometry electrochemical methods, and results revealed that PPyox-CFE improved the detection limit of DA. In particular, the sensitivity of DA was improved to 24.55 µA·µM−1·µm−2 using the PPyox-CFE. The ultramicrodic electrode combined with the patch-clamp system was used to detect vesicular exocytosis of DA from individual PC12 cells with 60 mM K+ stimulation. A total of 287 spikes released from 7 PC12 cells were statistically analyzed. The current amplitude (Imax and the released charge (Q of the amperometric spikes from the DA release by a stimulated PC12 cell is 45.1 ± 12.5 pA and 0.18 ± 0.04 pC, respectively. Furthermore, on average ~562,000 molecules were released in each vesicular exocytosis. PPyox-CFE, with its capability of detecting vesicular exocytosis, has potential application in neuron communication research.

Retrospective analysis of patients clinical manifestations before and after pheochromocytoma surgery.

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Balazovjech, I; Davidova, H; Breza, J

2004-01-01

A retrospective analysis of presurgical clinical picture and blood pressures of 34 patients with histologically verified pheochromocytoma. Assessment of clinical state, blood pressure and prognosis in the course of patients control hospitalizations from 2001 to 2002. The study was designed as a synoptic one, based on a retrospective analysis of 34 patients records with histologically verified pheochromocytoma (26 women and 8 men). Our assessments of clinical symptomatology, maximum paroxysmal hypertension values, average blood pressure values in patients with persistent arterial hypertension, arterial hypertension grade and circadian index were based on patients records. Patients epinephrectomies were followed during their control hospitalizations to assess their clinical state. Their blood pressures were evaluated by means of their circadian monitoring. From the 34 patients, 21 were diagnosed with solitary pheochromocytomas. The circadian index persistence analysis prior to the surgery was associated with circadian blood pressure monitoring in 21 patients. It was lost in 57% of patients. During their control hospitalization as many as 82% of patients preserved their circadian blood pressure variability with a more than 10% decrease in the night time, 5 patients did not preserve their circadian blood pressure variability. Seven from the original 34 patients died: Three of them died from their primary disease, one 63-year old man died from shock following tumour extirpation. The death of other 3 patients was not associated with their primary disease. Long-lasting survival of patients with pheochromocytoma after surgical treatment--except for those with malignant disease--was demonstrated. Although our assessment of the resulting treatment effects was positive, a long-term follow-up is inevitable because of a difficult pathologic-anatomical verification of the malignant nature of the disease as well as of the risk of tumour relapse assessment. (Tab. 1, Fig. 5, Ref 36.)

Pitfalls in genetic analysis of pheochromocytomas/paragangliomas-case report.

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Canu, Letizia; Rapizzi, Elena; Zampetti, Benedetta; Fucci, Rossella; Nesi, Gabriella; Richter, Susan; Qin, Nan; Giachè, Valentino; Bergamini, Carlo; Parenti, Gabriele; Valeri, Andrea; Ercolino, Tonino; Eisenhofer, Graeme; Mannelli, Massimo

2014-07-01

About 35% of patients with pheochromocytoma/paraganglioma carry a germline mutation in one of the 10 main susceptibility genes. The recent introduction of next-generation sequencing will allow the analysis of all these genes in one run. When positive, the analysis is generally unequivocal due to the association between a germline mutation and a concordant clinical presentation or positive family history. When genetic analysis reveals a novel mutation with no clinical correlates, particularly in the presence of a missense variant, the question arises whether the mutation is pathogenic or a rare polymorphism. We report the case of a 35-year-old patient operated for a pheochromocytoma who turned out to be a carrier of a novel SDHD (succinate dehydrogenase subunit D) missense mutation. With no positive family history or clinical correlates, we decided to perform additional analyses to test the clinical significance of the mutation. We performed in silico analysis, tissue loss of heterozygosity analysis, immunohistochemistry, Western blot analysis, SDH enzymatic assay, and measurement of the succinate/fumarate concentration ratio in the tumor tissue by tandem mass spectrometry. Although the in silico analysis gave contradictory results according to the different methods, all the other tests demonstrated that the SDH complex was conserved and normally active. We therefore came to the conclusion that the variant was a nonpathogenic polymorphism. Advancements in technology facilitate genetic analysis of patients with pheochromocytoma but also offer new challenges to the clinician who, in some cases, needs clinical correlates and/or functional tests to give significance to the results of the genetic assay.

Pheochromocytoma of posterior mediastinum (paraaortic paraganglioma). Report of a case and revision of the literature

International Nuclear Information System (INIS)

Rodriguez Sabogal, Carlos A; Pedrozo Pupo, John C; Ojeda Leon, Paulina; Garcia-Herreros, D Luis G; Fernandez, Federico

2000-01-01

Pheochromocytomas are a rare tumor, but it's important to know how to diagnose and treat them, because they are a potentially life-threatening disease that if recognized early by the physician can be managed with minimal morbidity. It constitutes one of few curable causes of arterial hypertension by performing surgical resection of the tumor. We report our experience with a female who has a pheochromocytoma in the posterior mediastinum

ADC histogram analysis for adrenal tumor histogram analysis of apparent diffusion coefficient in differentiating adrenal adenoma from pheochromocytoma.

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Umanodan, Tomokazu; Fukukura, Yoshihiko; Kumagae, Yuichi; Shindo, Toshikazu; Nakajo, Masatoyo; Takumi, Koji; Nakajo, Masanori; Hakamada, Hiroto; Umanodan, Aya; Yoshiura, Takashi

2017-04-01

To determine the diagnostic performance of apparent diffusion coefficient (ADC) histogram analysis in diffusion-weighted (DW) magnetic resonance imaging (MRI) for differentiating adrenal adenoma from pheochromocytoma. We retrospectively evaluated 52 adrenal tumors (39 adenomas and 13 pheochromocytomas) in 47 patients (21 men, 26 women; mean age, 59.3 years; range, 16-86 years) who underwent DW 3.0T MRI. Histogram parameters of ADC (b-values of 0 and 200 [ADC 200 ], 0 and 400 [ADC 400 ], and 0 and 800 s/mm 2 [ADC 800 ])-mean, variance, coefficient of variation (CV), kurtosis, skewness, and entropy-were compared between adrenal adenomas and pheochromocytomas, using the Mann-Whitney U-test. Receiver operating characteristic (ROC) curves for the histogram parameters were generated to differentiate adrenal adenomas from pheochromocytomas. Sensitivity and specificity were calculated by using a threshold criterion that would maximize the average of sensitivity and specificity. Variance and CV of ADC 800 were significantly higher in pheochromocytomas than in adrenal adenomas (P histogram parameters for diagnosing adrenal adenomas (ADC 200 , 0.82; ADC 400 , 0.87; and ADC 800 , 0.92), with sensitivity of 84.6% and specificity of 84.6% (cutoff, ≤2.82) with ADC 200 ; sensitivity of 89.7% and specificity of 84.6% (cutoff, ≤2.77) with ADC 400 ; and sensitivity of 94.9% and specificity of 92.3% (cutoff, ≤2.67) with ADC 800 . ADC histogram analysis of DW MRI can help differentiate adrenal adenoma from pheochromocytoma. 3 J. Magn. Reson. Imaging 2017;45:1195-1203. © 2016 International Society for Magnetic Resonance in Medicine.

Regulation of Taurine transporter activity in cultured rat retinal ganglion cells and rat retinal Muller Cells

International Nuclear Information System (INIS)

Eissa, Laila A.; Smith, Sylvia B.; El-sherbeny, Amira A.

2006-01-01

Diabetic retinopathy is one of the most common complications of diabetes. The amino acid taurine is believed to play an antioxidant protective role in diabetic retinopathy through the scavenging of the reactive species. It is not well established whether taurine uptake is altered in retina cells during diabetic conditions. Thus, the present study was designed to investigate the changes in taurine transport in cultures of rat retinal Muller cells and rat retinal ganglion cells under conditions associated with diabetes. Taurine was abundantly taken up by retinal Muller cells and rat retinal ganglion cells under normal glycemic condition. Taurine was actively transported to rat Muller cells and rat retinal ganglion cells in a Na and Cl dependant manner. Taurine uptake further significantly elevated in both type of cells after the incubation with high glucose concentration. This effect could be attributed to the increase in osmolarity. Because Nitric Oxide (NO) is a molecule implicated in the pathogenesis of diabetes, we also determined the activity of taurine transporter in cultured rat retinal Muller cells and rat retinal ganglion cells in the presence of the NO donors, SIN-1 and SNAP. Taurine uptake was elevated above control value after 24-h incubation with low concentration of NO donors. We finally investigated the ability of neurotoxic glutamate to change taurine transporter activity in both types of cells. Uptake of taurine was significantly increased in rat retinal ganglion cells when only incubated with high concentration of glutamate. Our data provide evidence that taurine transporter is present in cultured rat retinal ganglion and Muller cells and is regulated by hyperosmolarity. The data are relevant to disease such as diabetes and neuronal degeneration where retinal cell volume may dramatically change. (author)

Measurement of fractionated plasma metanephrines for exclusion of pheochromocytoma: Can specificity be improved by adjustment for age?

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Gafni Amiram

2005-02-01

Full Text Available Abstract Background Biochemical testing for pheochromocytoma by measurement of fractionated plasma metanephrines is limited by false positive rates of up to 18% in people without known genetic predisposition to the disease. The plasma normetanephrine fraction is responsible for most false positives and plasma normetanephrine increases with age. The objective of this study was to determine if we could improve the specificity of fractionated plasma measurements, by statistically adjusting for age. Methods An age-adjusted metanephrine score was derived using logistic regression from 343 subjects (including 33 people with pheochromocytoma who underwent fractionated plasma metanephrine measurements as part of investigations for suspected pheochromocytoma at Mayo Clinic Rochester (derivation set. The performance of the age-adjusted score was validated in a dataset of 158 subjects (including patients 23 with pheochromocytoma that underwent measurements of fractionated plasma metanephrines at Mayo Clinic the following year (validation dataset. None of the participants in the validation dataset had known genetic predisposition to pheochromocytoma. Results The sensitivity of the age-adjusted metanephrine score was the same as that of traditional interpretation of fractionated plasma metanephrine measurements, yielding a sensitivity of 100% (23/23, 95% confidence interval [CI] 85.7%, 100%. However, the false positive rate with traditional interpretation of fractionated plasma metanephrine measurements was 16.3% (22/135, 95% CI, 11.0%, 23.4% and that of the age-adjusted score was significantly lower at 3.0% (4/135, 95% CI, 1.2%, 7.4% (p Conclusion An adjustment for age in the interpretation of results of fractionated plasma metanephrines may significantly decrease false positives when using this test to exclude sporadic pheochromocytoma. Such improvements in false positive rate may result in savings of expenditures related to confirmatory imaging.

Pheochromocytoma complicated by intracerebral hemorrhage - a case report

International Nuclear Information System (INIS)

Nogueira, Aline Silva; Marchiori, Edson; Almeida, Fabiola Assuncao de; Martins, Renata Romano; Sales, Anderson Ribeiro; Santos, Tereza Cristina C.R.S. dos; Reis, Simone Teixeira; Silveira, Sonia Marcelino T. da

1999-01-01

The authors report a case of pheochromocytoma that was complicated by intracerebral hemorrhage in a 17-year-old female patient. Computed tomography showed a solid mass, heterogeneous, on the right adrenal. The patient underwent a right adrenalectomy. She is being observed by our out-patients clinic, presenting normal blood pressure levels and a left hemiparesis. (author)

Non-classical nuclear localization signal peptides for high efficiency lipofection of primary neurons and neuronal cell lines.

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Ma, H; Zhu, J; Maronski, M; Kotzbauer, P T; Lee, V M-Y; Dichter, M A; Diamond, S L

2002-01-01

Gene transfer into CNS is critical for potential therapeutic applications as well as for the study of the genetic basis of neural development and nerve function. Unfortunately, lipid-based gene transfer to CNS cells is extremely inefficient since the nucleus of these post-mitotic cells presents a significant barrier to transfection. We report the development of a simple and highly efficient lipofection method for primary embryonic rat hippocampal neurons (up to 25% transfection) that exploits the M9 sequence of the non-classical nuclear localization signal of heterogeneous nuclear ribonucleoprotein A1 for targeting beta(2)-karyopherin (transportin-1). M9-assistant lipofection resulted in 20-100-fold enhancement of transfection over lipofection alone for embryonic-derived retinal ganglion cells, rat pheochromocytoma (PC12) cells, embryonic rat ventral mesencephalon neurons, as well as the clinically relevant human NT2 cells or retinoic acid-differentiated NT2 neurons. This technique can facilitate the implementation of promoter construct experiments in post-mitotic cells, stable transformant generation, and dominant-negative mutant expression techniques in CNS cells.

A Case of Malignant Pheochromocytoma Detected during Fertility Treatment

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Kazuhisa Hagiwara

2014-01-01

Full Text Available We report a case of malignant pheochromocytoma in a 35-year-old Japanese woman during fertility treatment, successfully treated with surgical excision. The patient recovered without any postoperative problems, and plasma catecholamine levels normalized. At present, 18 months after the operation, there are no signs of relapse.

Pheochromocytoma-paraganglioma: Biochemical and genetic diagnosis.

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Cano Megías, Marta; Rodriguez Puyol, Diego; Fernández Rodríguez, Loreto; Sención Martinez, Gloria Lisette; Martínez Miguel, Patricia

Pheochromocytomas and paragangliomas are tumours derived from neural crest cells, which can be diagnosed by biochemical measurement of metanephrine and methoxytyramine. Advances in genetic research have identified many genes involved in the pathogenesis of these tumours, suggesting that up to 35-45% may have an underlying germline mutation. These genes have a singular transcriptional signature and can be grouped into 2 clusters (or groups): cluster 1 (VHL and SHDx), involved in angiogenesis and hypoxia pathways; and cluster 2 (MEN2 and NF1), linked to the kinase signalling pathway. In turn, these genes are associated with a characteristic biochemical phenotype (noradrenergic and adrenergic), and clinical features (location, biological behaviour, age of presentation, etc.) in a large number of cases. Early diagnosis of these tumours, accompanied by a correct genetic diagnosis, should eventually become a priority to enable better treatment, early detection of complications, proper screening of family members and related tumours, as well as an improvement in the overall prognosis of these patients. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Unexpected visitor on FDG PET/CT--brown adipose tissue (BAT) in mesentery in a case of retroperitoneal extra-adrenal pheochromocytoma: is the BAT activation secondary to catecholamine-secreting pheochromocytoma?

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Joshi, Prathamesh Vijay; Lele, Vikram Ramchandra

2012-05-01

Fused positron emission tomography-computed tomography (PET/CT) technology has enabled the determination that nonmalignant fluorodeoxyglucose (FDG) uptake is observed in brown adipose tissue (BAT). FDG uptake in BAT is a known potential source of false-positive interpretations for PET. The typical locations of BAT include neck, supraclavicular area, mediastinum, and paravertebral intercostal spaces. Examples of atypical locations for BAT include posterior neck, left paratracheal area, axillae, perirenal area, and retrocrural area. We report PET/CT findings in a young male patient with malignant retroperitoneal extra-adrenal pheochromocytoma, who demonstrated FDG uptake in BAT at multiple locations including mesenteric BAT. We also propose catecholamine-secreting pheochromocytoma as a possible cause of BAT activation in our case.

A Rare Cause of Pheochromocytoma; Neurofibromatosis Type 1-Noonan Syndrome

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Mazhar Müslüm Tuna

2014-09-01

Full Text Available Neurofibromatosis (NF Type 1 (NF-1 is an autosomal dominant disease with a prevalence of about 1/3000. NF-1 is a neurocutaneous syndrome characterized by cafe au lait macules, neurofibroma, optic glioma, lisch nodules, and symptoms involving other systems. Noonan syndrome (NS is a clinically heterogeneous disorder predominantly characterized by dysmorphic facial features, congenital heart disease, proportionate post-natal short stature, neck abnormalities, and chest deformities. NF-NS is a very rare overlapping syndrome sharing many features of both syndromes. Coexistence of pheochromocytoma, which can be life-threatening if not treated properly, is also a very rare complication of this disorder. Here, we report a patient who was admitted with a mass in the right upper quadrant and was diagnosed with pheochromocytoma and NFNS. (The Me­di­cal Bul­le­tin of Ha­se­ki 2014; 52: 227-31

The Traditional Japanese Herbal Medicine Hachimijiogan Elicits Neurite Outgrowth Effects in PC12 Cells and Improves Cognitive in AD Model Rats via Phosphorylation of CREB

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Kaori Kubota

2017-11-01

Full Text Available Hachimijiogan (HJG is a traditional herbal medicine that improves anxiety disorders in patients with dementia. In this study, we tested the hypothesis that HJG exerts neurotrophic factor-like effects to ameliorate memory impairment in Alzheimer disease (AD model rats. First, we describe that HJG acts to induce neurite outgrowth in PC12 cells (a rat pheochromocytoma cell line like nerve growth factor (NGF in a concentration-dependent manner (3 μg/ml HJG, p < 0.05; 10–500 μg/ml HJG, p < 0.001. While six herbal constituents of HJG, Rehmannia root, Dioscorea rhizome, Rhizoma Alismatis, Poria sclerotium, Moutan bark, and Cinnamon bark, could induce neurite outgrowth effects, the effect was strongest with HJG (500 μg/ml. Second, we demonstrated that HJG-induced neurite outgrowth was blocked by an inhibitor of cAMP response element binding protein (CREB, KG-501 (10 μM, p < 0.001. Moreover, HJG was observed to induce CREB phosphorylation 20–90 min after treatment (20 min, 2.50 ± 0.58-fold and CRE-mediated transcription in cultured PC12 cells (500 μg/ml, p < 0.01; 1000 μg/ml, p < 0.001. These results suggest a CREB-dependent mechanism underlies the neurotrophic effects of HJG. Finally, we examined improvements of memory impairment following HJG treatment using a Morris water maze in AD model animals (CI + Aβ rats. Repeated oral administration of HJG improved memory impairment (300 mg/kg, p < 0.05; 1000 mg/kg, p < 0.001 and induced CREB phosphorylation within the hippocampus (1000 mg/kg, p < 0.01. Together, our results suggest that HJG possesses neurotrophic effects similar to those of NGF, and can ameliorate cognitive dysfunction in a rat dementia model via CREB activation. Thus, HJG could potentially be a substitute for neurotrophic factors as a treatment for dementia.

Pheochromocytoma as a rare cause of hypertension in a 46 X, i(X)(q10) turner syndrome: a case report and literature review.

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Shin, Ji Yeon; Kim, Bo Hyun; Kim, Young Keum; Kim, Tae Hwa; Kim, Eun Heui; Lee, Min Jin; Kim, Jong Ho; Jeon, Yun Kyung; Kim, Sang Soo; Kim, In Joo

2018-05-10

Cardiovascular disease (CVD) presents the most serious health problems and contributes to the increased mortality in young women with Turner syndrome. Arterial hypertension in Turner syndrome patients is significantly more prevalent than that in a general age-matched control group. The aetiology of hypertension in Turner syndrome varies, even in the absence of cardiac anomalies and obvious structural renal abnormalities. Pheochromocytoma is an extremely rare cause among various etiologies for hypertension in patients with Turner syndrome. Here, we reported a pheochromocytoma as a rare cause of hypertension in Turner syndrome patient. A 21-year-old woman who has diagnosed with Turner syndrome with a karyotype of 46,X,i(X)(q10) visited for hypertension and mild headache. Transthoracic echography (TTE) showed no definite persistent ductus arteriosus shunt flow and cardiac valve abnormalities. Considering other important secondary causes like pheochromocytoma, hormonal studies were performed and the results showed increased serum norepinephrine, serum normetanephrine, and 24 h urine norepinephrine. We performed an abdominal computed tomography (CT) to confirm the location of pheochromocytoma. Abdominal CT showed a 1.9 cm right adrenal mass. I-131 meta-iodobenzylguanidine (MIBG) scintigraphy showed a right adrenal uptake. Laparoscopic adrenalectomy was performed and confirmed a pheochromocytoma. After surgery, blood pressure was within normal ranges and postoperative course was uneventful, and no recurrence developed via biochemical tests and abdominal CT until 24 months. Our case and previous literatures suggest that hypertension caused by pheochromocytoma which is a rare but important and potentially lethal cause of hypertension in Turner syndrome. This case underlines the importance of early detection of pheochromocytoma in Turner syndrome. Clinicians should keep in mind that pheochromocytoma can be a cause of hypertension in patients with Turner syndrome.

Bone Resorption Is Increased in Pheochromocytoma Patients and Normalizes following Adrenalectomy

NARCIS (Netherlands)

Veldhuis-Vlug, A.G.; El Mahdiui, M.; Endert, E.; Heijboer, A.C.; Fliers, E.; Bisschop, P.H.

2012-01-01

Context: The sympathetic nervous system (SNS) controls bone turnover in rodents, but it is uncertain whether a similar role for the SNS exists in humans. Pheochromocytomas are catecholamine-producing neuroendocrine tumors. Because catecholamines are the neurotransmitters of the SNS, we hypothesized

Clinical and laboratory features of pheochromocytoma in a 52-year-old female patient

Directory of Open Access Journals (Sweden)

Otmara Aranguren Barreto

2014-04-01

Full Text Available The article aims to describe the clinical and laboratory features of a female patient suffering from pheochromocytoma. The case is a 52-year-old female patient who presents to our healthcare center with high blood pressure, cold limbs, sweating, jitteriness, and episodes of oppressive chest pain that appear several times per day. She also reports fatigue and a 13-kilogram weight loss. The sonogram revealed a nodular image in the right adrenal gland that had low echogenicity and regular margins measuring 5 mm. The image was confirmed with a contrast-enhanced adrenal CAT scan. Urine vanillylmandelic acid levels were high and an adrenal biopsy confirmed a pheochromocytoma measuring 4.5 x 3.5 x 3 cm.

The radioenzymatic determination of adrenaline and noradrenaline in plasma and its use in the diagnostic of pheochromocytomas

International Nuclear Information System (INIS)

Neuhaus, C.P.E.

1982-01-01

The radioenzymatic determination of adrenaline and noradrenaline in human plasma for the diagnosis of pheochromocytomas was put to use after improvements were made with respect to extraction and separation steps. The plasma catecholamines at rest were distinctly higher in patients with pheochromocytomas. The plasma catecholamine level showed a significant increase as well with the glucagon test between the second and fifth minute. The method was not well suited for the localisation diagnostic where the plasma catecholamines were determined in selectively taken blood from the lower vena cava. Overall, however, the radioenzymatic determination of catecholamines in plasma proved itself to be a relatively ponderous, but exact and sensitive method for the measuring of basal catecholamine level and its changes. In the clinical area it is used as a valuable supplement to the contemporary diagnostic of pheochromocytomas. (orig./TRV) [de

A systematic review of the literature examining the diagnostic efficacy of measurement of fractionated plasma free metanephrines in the biochemical diagnosis of pheochromocytoma

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Thabane Lehana

2004-06-01

Full Text Available Abstract Background Fractionated plasma metanephrine measurements are commonly used in biochemical testing in search of pheochromocytoma. Methods We aimed to critically appraise the diagnostic efficacy of fractionated plasma free metanephrine measurements in detecting pheochromocytoma. Nine electronic databases, meeting abstracts, and the Science Citation Index were searched and supplemented with previously unpublished data. Methodologic and reporting quality was independently assessed by two endocrinologists using a checklist developed by the Standards for Reporting of Diagnostic Studies Accuracy Group and data were independently abstracted. Results Limitations in methodologic quality were noted in all studies. In all subjects (including those with genetic predisposition: the sensitivities for detection of pheochromocytoma were 96%–100% (95% CI ranged from 82% to 100%, whereas the specificities were 85%–100% (95% CI ranged from 78% to 100%. Statistical heterogeneity was noted upon pooling positive likelihood ratios when those with predisposition to disease were included (p Conclusion Negative plasma fractionated free metanephrine measurements are effective in ruling out pheochromocytoma. However, a positive test result only moderately increases suspicion of disease, particularly when screening for sporadic pheochromocytoma.

Recurrence of pheochromocytoma in 11 years old school child, diagnosed by I-131 MIBG

International Nuclear Information System (INIS)

Jara Yorg, J. A; Arias, Cohl; Gimenez, J; Rodriguez, E; Ortiz, L; Mendieta, B; Ayala, R. M; Rodriguez, C; Delgadillo, J. L

2000-01-01

Pheocromocytoma is a paraganglioma with an incidence of arterial hypertension approximately of 1%,but its diagnosis has several important issues from the clinical point of view. 1-The tumor resection frequently cure the hypertension. 2.-Its manifestations might simulates other diseases like carcinoid Sx, hypertiroidism,etc. 3.-It is a familiar disease transmitted by an autosomic dominant way. It is 10% bilateral,10%extraadrenal,10% occur in children and 10% are malignant. We present a case of pheochromocytoma recurrency in a young girl,11 y.o. operated 8 months before, at the Clinical Hospital, National University of Paraguay, School of Medicine for a right suprarenal gland pheochromocytoma of 2cms of diameter, who consults the Pediatric Department for arterial hypertension and cefalea. She also had a Von Hippel Sx and Glaucoma. Nuclear Medicine is a non invasive method that use the I-131 Methayodobencylguanidine(MIBG-I-131) with high accuracy to diagnose and treat both neuroblastoma and pheochromocytoma I-131 MIBG is the gold standard for the diagnosis of both entities with a sensitivity between 94-100%6-7 and specificity of 100% being the best method to evaluate these diseases in the pre and post operatory (Au)

Magnesium sulphate and (123)I-MIBG in pheochromocytoma: Two useful techniques for a complicated disease.

Science.gov (United States)

Vendrell, M; Martín, N; Tejedor, A; Ortiz, J T; Muxí, À; Taurà, P

2016-01-01

Pheochromocytoma is a tumour of the chromaffin tissue. It may, through catecholamine release, have deleterious effects on myocardial structure. A 48-year-old woman with a history of hypertension and type II diabetes mellitus (ASA II) was diagnosed of pheochromocytoma-induced myocarditis, which caused severe cardiogenic shock, with an ejection fraction of 20%. Extreme blood pressure swings required aggressive therapy with vasoactive drugs (norepinephrine and dopamine) and an intra-aortic balloon pump, despite which severe haemodynamic instability persisted. Finally, the use of magnesium sulphate allowed for cardiovascular stabilization and weaning off vasoactive drugs prior to surgery. (123)I-metaiodobenzylguanidine scintigraphy helps not only to functionally confirm tumour tissue, but also to assess severity and prognosis of cardiac failure. Prognosis of pheochromocytoma-induced heart failure can be very poor. The use of these two well-known and relatively simple 'tools' for treatment and prognosis is a helpful option to keep in mind. Copyright © 2014 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

ACTH-producing pheochromocytoma: clinical considerations and concise review of the literature

NARCIS (Netherlands)

Nijhoff, M. F.; Dekkers, O. M.; Vleming, L. J.; Smit, J. W. A.; Romijn, J. A.; Pereira, A. M.

2009-01-01

We present a patient with a rare cause of ectopic ACTH-dependent Cushing's syndrome, caused by a pheochromocytoma. The case provides clues for a detailed discussion on the pitfalls and diagnostic difficulties in establishing the correct underlying cause of ACTH-dependent Cushing's syndrome. It

A retrospective study of secondary diabetes prevalence in Pheochromocytoma, Cushing and Acromegal patients

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Bastan Hagh M

1997-07-01

Full Text Available Some of the endocrinologic diseases, especially Acromegaly, Cushing and Pheochromocytoma have multiple effects on blood glucose metabolism and regulation in non-diabetic patients. In this retrospective survey, records of patients of Tehran Medical Sciences University hospitals have been reviewd. Of 124 Acromegals, GTT was performed for 51 patients, being impaired in 18%. To evaluate diabetes, FBS and BS of 90 patients were checked, overt diabetes was detected in 27%. Among 90 Cushing patients, blood glucose was checked in 60 cases, 47% of these patients had levels above the normal range, and 39% had glucosuria. Among 80 Pheochromocytoma patients, 16 cases (26.5% had overt diabetes. In comparison with other studied, we have obtained a little different results concerning diabetes and impaired GTT prevalence

Effect of early adrenal vein ligation on blood pressure and catecholeamine fluctuation during laparoscopic adrenalectomy for pheochromocytoma.

Science.gov (United States)

Wu, Guojun; Zhang, Bo; Yu, Chuigong; Gao, Lei; Gao, Yang; Huang, Yi; Yu, Lei; Zhang, Geng; Yang, Lijun; Yuan, Jianlin

2013-09-01

To define whether previous control of the adrenal vein is a crucial procedure in laparoscopic adrenalectomy for pheochromocytoma. From January 2000 to December 2010, 114 patients with pheochromocytoma who underwent laparoscopic adrenalectomy through transperitoneal or retroperitoneal approach were included. The patients were divided into 2 groups randomly (group 1: dissection after ligation; group 2: dissection before ligation). Blood samples for the measurement of catecholamines levels using high performance liquid chromatography were taken at the following time points: t1, before anesthesia; t2, during manipulation-extraction of pheochromocytoma; t3, after removal of pheochromocytoma. The blood pressure fluctuation was recorded. Laparoscopic adrenalectomy was successfully performed on 113 patients with 1 elective open conversion because of dense peritumor adhesions. The operating time ranged from 80 to 150 minutes (mean 108, 102 in group 1, 110 in group 2). Mean blood loss ranged from 20 to 500 mL (mean 120 mL, 110 in group 1, 125 in group 2). The concentrations of plasma catecholamines between the 2 groups had no statistical differences. The blood pressure fluctuation incidence between the 2 groups had no marked difference. But the incidence increased with high functionary grade, and the difference was significant (P = .043). This study demonstrated that previous control of the adrenal vein was not a determinate factor in dealing with dangerous hypertension during laparoscopic adrenalectomies. Copyright © 2013 Elsevier Inc. All rights reserved.

Beckwith-Wiedemann syndrome and bilateral adrenal pheochromocytoma: sonography and MRI findings

Energy Technology Data Exchange (ETDEWEB)

Baldisserotto, Matteo; Peletti, Adriana Barcellos; Araujo, Manoel Angelo de; Pertence, Ana Paula Cardoso; Dora, Marcelo Dourado; Maciel, Elines Oliva; Gaiger, Ana Maria [Hospital da Crianca Conceicao, Departamento de Radiologia, Porto Alegre, RS (Brazil)

2005-11-01

Beckwith-Wiedemann syndrome is characterized by a group of clinical abnormalities, the most frequent of which are omphalocele, macroglossia, gigantism, neonatal hypoglycemia and umbilical hernia. The association of this syndrome with malignant tumors is well documented. We report a child with this syndrome associated with bilateral adrenal pheochromocytoma. (orig.)

Beckwith-Wiedemann syndrome and bilateral adrenal pheochromocytoma: sonography and MRI findings

International Nuclear Information System (INIS)

Baldisserotto, Matteo; Peletti, Adriana Barcellos; Araujo, Manoel Angelo de; Pertence, Ana Paula Cardoso; Dora, Marcelo Dourado; Maciel, Elines Oliva; Gaiger, Ana Maria

2005-01-01

Beckwith-Wiedemann syndrome is characterized by a group of clinical abnormalities, the most frequent of which are omphalocele, macroglossia, gigantism, neonatal hypoglycemia and umbilical hernia. The association of this syndrome with malignant tumors is well documented. We report a child with this syndrome associated with bilateral adrenal pheochromocytoma. (orig.)

The first Dutch SDHB founder deletion in paraganglioma – pheochromocytoma patients

Directory of Open Access Journals (Sweden)

Devilee Peter

2009-04-01

Full Text Available Abstract Background Germline mutations of the tumor suppressor genes SDHB, SDHC and SDHD play a major role in hereditary paraganglioma and pheochromocytoma. These three genes encode subunits of succinate dehydrogenase (SDH, the mitochondrial tricarboxylic acid cycle enzyme and complex II component of the electron transport chain. The majority of variants of the SDH genes are missense and nonsense mutations. To date few large deletions of the SDH genes have been described. Methods We carried out gene deletion scanning using MLPA in 126 patients negative for point mutations in the SDH genes. We then proceeded to the molecular characterization of deletions, mapping breakpoints in each patient and used haplotype analysis to determine whether the deletions are due to a mutation hotspot or if a common haplotype indicated a single founder mutation. Results A novel deletion of exon 3 of the SDHB gene was identified in nine apparently unrelated Dutch patients. An identical 7905 bp deletion, c.201-4429_287-933del, was found in all patients, resulting in a frameshift and a predicted truncated protein, p.Cys68HisfsX21. Haplotype analysis demonstrated a common haplotype at the SDHB locus. Index patients presented with pheochromocytoma, extra-adrenal PGL and HN-PGL. A lack of family history was seen in seven of the nine cases. Conclusion The identical exon 3 deletions and common haplotype in nine patients indicates that this mutation is the first Dutch SDHB founder mutation. The predominantly non-familial presentation of these patients strongly suggests reduced penetrance. In this small series HN-PGL occurs as frequently as pheochromocytoma and extra-adrenal PGL.

Update on Modern Management of Pheochromocytoma and Paraganglioma

Directory of Open Access Journals (Sweden)

Jacques W. M. Lenders

2017-06-01

Full Text Available Despite all technical progress in modern diagnostic methods and treatment modalities of pheochromocytoma/paraganglioma, early consideration of the presence of these tumors remains the pivotal link towards the best possible outcome for patients. A timely diagnosis and proper treatment can prevent the wide variety of potentially catastrophic cardiovascular complications. Modern biochemical testing should include tests that offer the best available diagnostic performance, measurements of metanephrines and 3-methoxytyramine in plasma or urine. To minimize false-positive test results particular attention should be paid to pre-analytical sampling conditions. In addition to anatomical imaging by computed tomography (CT or magnetic resonance imaging, new promising functional imaging modalities of photon emission tomography/CT using with somatostatin analogues such as 68Ga-DOTATATE (68Ga-labeled DOTA(0-Tyr(3-octreotide will probably replace 123I-MIBG (iodine-123-metaiodobenzylguanidine in the near future. As nearly half of all pheochromocytoma patients harbor a mutation in one of the 14 tumor susceptibility genes, genetic testing and counseling should at least be considered in all patients with a proven tumor. Post-surgical annual follow-up of patients by measurements of plasma or urinary metanephrines should last for at least 10 years for timely detection of recurrent or metastatic disease. Patients with a high risk for recurrence or metastatic disease (paraganglioma, young age, multiple or large tumors, genetic background should be followed up lifelong.

Embolisation of pheochromocytoma to stabilise and wean a patient in cardiogenic shock from emergency extracorporeal life support

DEFF Research Database (Denmark)

Vagner, Helle; Hey, Thomas Morris; Elle, Bo

2015-01-01

Pheochromocytoma is a catecholamine-secreting tumour associated with varying symptoms ranging from episodic headache, sweating, paroxysmal hypertension and tachycardia to intractable cardiogenic shock. Cardiogenic shock is rare but well-described and the timing of correct management is crucial si...... since mortality is high. Fifty per cent of pheochromocytomas are diagnosed on autopsy. We report on a case of embolisation of the adrenal artery during ongoing extracorporeal life support (ECLS) in order to stabilise and wean the patient from ECLS as a bridge to final surgery....

Novel Preclinical Testing Strategies for Treatment of Metastatic Pheochromocytoma

Science.gov (United States)

2015-11-01

Schleswig-Holstein Lübeck, Lübeck, Germany Abstract There is currently no effective treatment for metastatic pheochromocytomas and paragangliomas. A...Supplementary Fig. S2) and deregulated fatty acid metabolism (Fig. 2b), leading to higher levels of palmitate and linoleate, increased long chain fatty...mitochondria18. This pathway required HIF-1a, which is deregulated in SDHB-mutant tumours, and may potentially contribute to disease maintenance39. The

Pheochromocytoma presenting as an acute coronary syndrome complicated by acute heart failure: The challenge of a great mimic.

Science.gov (United States)

Sanna, Giuseppe Damiano; Talanas, Giuseppe; Fiore, Giuseppina; Canu, Antonella; Terrosu, Pierfranco

2016-10-01

Pheochromocytoma is a rare neuroendocrine tumor with a highly variable clinical presentation. The serious and potentially lethal cardiovascular complications of these tumors are related to the effects of secreted catecholamines. We describe a case of a 50-year-old woman urgently admitted to our hospital because of symptoms and clinical and instrumental findings consistent with an acute coronary syndrome complicated by acute heart failure. Urgent coronary angiography showed normal coronary arteries. During her hospital stay, the recurrence of episodes characterized by a sudden increase in blood pressure, cold sweating, and nausea allowed us to hypothesize a pheochromocytoma. The diagnosis was confirmed by elevated levels of urinary catecholamines and by the finding of a left adrenal mass on magnetic resonance imaging. The patient underwent left adrenalectomy. Therefore, the initial diagnosis was critically reappraised and reviewed as a cardiac manifestation of a pheochromocytoma during catecholaminergic crisis.

Diurnal Blood Pressure Variation in Pheochromocytoma, Primary Aldosteronism and Cushing's Syndrome

Czech Academy of Sciences Publication Activity Database

Zelinka, T.; Štrauch, B.; Pecen, Ladislav; Widimský jr., J.

Roc. 18, c. 1 (2004), s. 107-111 ISSN 0950-9240 R&D Projects: GA MŠk LN00B107 Institutional research plan: CEZ:AV0Z1030915 Keywords : primary aldosteronism * pheochromocytoma * Cushing's syndrome * cirardian blood pressure rhythm Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 1.930, year: 2004

Noninvasive screening for pheochromocytoma in patients with an incidentally discovered adrenal mass. Usefulness of provocative test with metoclopramide and {sup 131}I-metaiodobenzylguanidine scintigraphy

Energy Technology Data Exchange (ETDEWEB)

Yokoyama, Hiroshi; Tsuji, Yuji [Fukuoka Univ. (Japan). School of Medicine

1999-10-01

Pheochromocytoma accounts for approximately 25% of incidentally discovered adrenal masses. Certain diagnostic procedures (e.g., adrenal arteriography, needle biopsy of an adrenal mass), anesthesia and abdominal surgery may cause a sudden release of catecholamines from a pheochromocytoma and induce paroxysmal attacks of hypertension. In addition, pheochromocytoma is well known to cause unsuspected operating room deaths. Therefore, we must carefully separate this functioning neoplasm from other types of adrenal masses. In this study, we compared the results of noninvasive tests including assay of urinary catecholamines and their metabolites, a provocative pharmacologic test using metoclopramide (MCP test), and {sup 131}I-metaiodobenzylguanidine (MlBG) scintigraphy to screen for pheochromocytoma in 10 consecutive patients with an incidentally discovered adrenal mass (6 pheochromocytomas and 4 non-functioning adrenocortical adenomas). We measured the 24-hour urinary excretion of catecholamines, metanephrines and vanillyl mandelic acid in all 10 patients; 5 were positive, 4 were negative and 1 was false-negative (sensitivity=83%, specificity=100%). The MCP test was performed in 7 patients; 3 were positive, 3 were negative and 1 was false-negative (sensitivity=75%, specificity=100%). MIBG scintigraphy was performed in 7 patients; 4 were positive, 1 was negative and 2 were false-negative (sensitivity=67%, specificity=100%). According to these results, all patients with an incidentally discovered adrenal mass should undergo a determination of the 24-hour urinary excretion of catecholamines and their metabolites, including metanephrines. If this urine assay is negative, other noninvasive tests including the MCP test and MIBG scintigraphy should be considered in selected patients with radiographic characteristics of pheochromocytoma. (author)

Pheochromocytoma/Paraganglioma: A Poster Child for Cancer Metabolism.

Science.gov (United States)

Tevosian, Sergei G; Ghayee, Hans K

2018-05-01

Pheochromocytomas (PCCs) are tumors that are derived from the chromaffin cells of the adrenal medulla. Extra-adrenal PCCs called paragangliomas (PGLs) are derived from the sympathetic and parasympathetic chain ganglia. PCCs secrete catecholamines, which cause hypertension and have adverse cardiovascular consequences as a result of catecholamine excess. PGLs may or may not produce catecholamines depending on their genetic type and anatomical location. The most worrisome aspect of these tumors is their ability to become aggressive and metastasize; there are no known cures for metastasized PGLs. Original articles and reviews indexed in PubMed were identified by querying with specific PCC/PGL- and Krebs cycle pathway-related terms. Additional references were selected through the in-depth analysis of the relevant publications. We primarily discuss Krebs cycle mutations that can be instrumental in helping investigators identify key biological pathways and molecules that may serve as biomarkers of or treatment targets for PCC/PGL. The mainstay of treatment of patients with PCC/PGLs is surgical. However, the tide may be turning with the discovery of new genes associated with PCC/PGLs that may shed light on oncometabolites used by these tumors.

Update on Modern Management of Pheochromocytoma and Paraganglioma.

Science.gov (United States)

Lenders, Jacques W M; Eisenhofer, Graeme

2017-06-01

Despite all technical progress in modern diagnostic methods and treatment modalities of pheochromocytoma/paraganglioma, early consideration of the presence of these tumors remains the pivotal link towards the best possible outcome for patients. A timely diagnosis and proper treatment can prevent the wide variety of potentially catastrophic cardiovascular complications. Modern biochemical testing should include tests that offer the best available diagnostic performance, measurements of metanephrines and 3-methoxytyramine in plasma or urine. To minimize false-positive test results particular attention should be paid to pre-analytical sampling conditions. In addition to anatomical imaging by computed tomography (CT) or magnetic resonance imaging, new promising functional imaging modalities of photon emission tomography/CT using with somatostatin analogues such as ⁶⁸Ga-DOTATATE (⁶⁸Ga-labeled DOTA(0)-Tyr(3)-octreotide) will probably replace ¹²³I-MIBG (iodine-123-metaiodobenzylguanidine) in the near future. As nearly half of all pheochromocytoma patients harbor a mutation in one of the 14 tumor susceptibility genes, genetic testing and counseling should at least be considered in all patients with a proven tumor. Post-surgical annual follow-up of patients by measurements of plasma or urinary metanephrines should last for at least 10 years for timely detection of recurrent or metastatic disease. Patients with a high risk for recurrence or metastatic disease (paraganglioma, young age, multiple or large tumors, genetic background) should be followed up lifelong. Copyright © 2017 Korean Endocrine Society.

Inhalation carcinogenicity study with nickel metal powder in Wistar rats

International Nuclear Information System (INIS)

Oller, Adriana R.; Kirkpatrick, Daniel T.; Radovsky, Ann; Bates, Hudson K.

2008-01-01

Epidemiological studies of nickel refinery workers have demonstrated an association between increased respiratory cancer risk and exposure to certain nickel compounds (later confirmed in animal studies). However, the lack of an association found in epidemiological analyses for nickel metal remained unconfirmed for lack of robust animal inhalation studies. In the present study, Wistar rats were exposed by whole-body inhalation to 0, 0.1, 0.4, and 1.0 mg Ni/m 3 nickel metal powder (MMAD = 1.8 μm, GSD = 2.4 μm) for 6 h/day, 5 days/week for up to 24 months. A subsequent six-month period without exposures preceded the final euthanasia. High mortality among rats exposed to 1.0 mg Ni/m 3 nickel metal resulted in the earlier termination of exposures in this group. The exposure level of 0.4 mg Ni/m 3 was established as the MTD for the study. Lung alterations associated with nickel metal exposure included alveolar proteinosis, alveolar histiocytosis, chronic inflammation, and bronchiolar-alveolar hyperplasia. No increased incidence of neoplasm of the respiratory tract was observed. Adrenal gland pheochromocytomas (benign and malignant) in males and combined cortical adenomas/carcinomas in females were induced in a dose-dependent manner by the nickel metal exposure. The incidence of pheochromocytomas was statistically increased in the 0.4 mg Ni/m 3 male group. Pheochromocytomas appear to be secondary to the lung toxicity associated with the exposure rather than being related to a direct nickel effect on the adrenal glands. The incidence of cortical tumors among 0.4 mg Ni/m 3 females, although statistically higher compared to the concurrent controls, falls within the historical control range; therefore, in the present study, this tumor is of uncertain relationship to nickel metal exposure. The lack of respiratory tumors in the present animal study is consistent with the findings of the epidemiological studies

PheoSeq : A Targeted Next-Generation Sequencing Assay for Pheochromocytoma and Paraganglioma Diagnostics

NARCIS (Netherlands)

Currás-Freixes, Maria; Piñeiro-Yañez, Elena; Montero-Conde, Cristina; Apellániz-Ruiz, María; Calsina, Bruna; Mancikova, Veronika; Remacha, Laura; Richter, Susan; Ercolino, Tonino; Rogowski-Lehmann, Natalie; Deutschbein, Timo; Calatayud, María; Guadalix, Sonsoles; Álvarez-Escolá, Cristina; Lamas, Cristina; Aller, Javier; Sastre-Marcos, Julia; Lázaro, Conxi; Galofré, Juan C.; Patiño-García, Ana; Meoro-Avilés, Amparo; Balmaña-Gelpi, Judith; De Miguel-Novoa, Paz; Balbín, Milagros; Matías-Guiu, Xavier; Letón, Rocío; Inglada-Pérez, Lucía; Torres-Pérez, Rafael; Roldán-Romero, Juan M.; Rodríguez-Antona, Cristina; Fliedner, Stephanie M J; Opocher, Giuseppe; Pacak, Karel; Korpershoek, Esther; de Krijger, Ronald R.; Vroonen, Laurent; Mannelli, Massimo; Fassnacht, Martin; Beuschlein, Felix; Eisenhofer, Graeme; Cascón, Alberto; Al-Shahrour, Fátima; Robledo, Mercedes

2017-01-01

Genetic diagnosis is recommended for all pheochromocytoma and paraganglioma (PPGL) cases, as driver mutations are identified in approximately 80% of the cases. As the list of related genes expands, genetic diagnosis becomes more time-consuming, and targeted next-generation sequencing (NGS) has

The Epidemiology of Pheochromocytoma: Increasing incidence and changing clinical presentation

DEFF Research Database (Denmark)

Ebbehoj, A; Søndergaard, Esben; Trolle, Christian

2017-01-01

–2015. In 1977–2006 paroxysmal symptoms and secondary hypertension were the primary causes leading to the diagnosis (34 and 21%, respectively), while incidentalomas were the leading cause of diagnosis 2007–2015 (57%). Patients diagnosed 2007–2015 were older (P... diagnosed in 1977–2006 in a secondary analysis using the Wilcoxon–Mann–Whitney test.We identified 183 confirmed cases of pheochromocytoma. A significant increasing trend (P

Mandibular metastasis presenting as the initial maifestation of malignant pheochromocytoma

Energy Technology Data Exchange (ETDEWEB)

Yanagi, Yoshinobu; Asaumi, Jun-ichi E-mail: asaumi@md.okayama-u.ac.jp; Hisatomi, Miki; Konouchi, Hironobu; Wakasa, Toru; Kishi, Kanji

2002-10-01

A case of 59-year-old male patient presenting with metastasis to the mandible from malignant pheochromocytoma is described. The conventional radiographs and CT images suggested that the lesion was malignant osteogenic tumors or metastatic tumors due to the existence of calcification and widesoread periosteal sunburst spiculation. On MRI, an expansive mass was clearly depicted and the signal intensities of the lesion were low to intermediate on T1 weighted image with intermediate to high signal intensity on T2 weighted image. A strong enhancement of the lesion was also observed on contrast enhanced T1 weighted image. On maximum intensity projection image in the arterial phase, the mass showed exceedingly early enhancement and excessively dislocated adjacent vessels. The diagnosis of a pheochromcytoma was difficult on the basis of these imagings. The final diagnosis was based on a biopsy of the mandible and I-131 Meta-iodobenzylguanidine scintigraphy (MIBG) scintigraphy. A primary lesion of the right adrenal showed low uptake due to wide centric necrosis and metastatic lesions of liver, lumber vertebrae, ribs and sacroiliac joint showed high uptake on the I-131 MIBG scintigraphy. The final diagnosis was nonfunctioning malignant pheochromocytoma due to the absence of elevation of catecholamine or its metabolite.

Cement-augmented dorsal instrumentation of the spine as a safe adjunct to the multimodal management of metastatic pheochromocytoma: a case report

Directory of Open Access Journals (Sweden)

Rittirsch Daniel

2012-01-01

Full Text Available Abstract Malignant pheochromocytoma is a neuroendocrine tumor that originates from chromaffin tissue. Although osseous metastases are common, metastatic dissemination to the spine rarely occurs. Five years after primary diagnosis of extra-adrenal, abdominal pheochromocytoma and laparoscopic extirpation, a 53-year old patient presented with recurrence of pheochromocytoma involving the spine, the pelvis, both proximal femora and the right humerus. Magnetic resonance imaging and computed tomography revealed osteolytic lesions of numerous vertebrae (T1, T5, T10, and T12. In the case of T10, total destruction of the vertebral body with involvement of the rear edge resulted in the risk of vertebral collapse and subsequent spinal stenosis. Thus, dorsal instrumentation (T8-T12 and cement augmentation of T12 was performed after perioperative alpha- and beta-adrenergic blockade with phenoxybenzamine and bisoprolol. After thorough preoperative evaluation to assess the risk for surgery and anesthesia, and appropriate perioperative management including pharmacological antihypertensive treatment, dorsal instrumentation of T8-T12 and cement augmentation of T12 prior to placing the corresponding pedicle screws did not result in hypertensive crisis or hemodynamic instability due to the release of catecholamines from metastatic lesions. To the authors' knowledge, this is the first report describing cement-augmentation in combination with dorsal instrumentation to prevent osteolytic vertebral collapse in a patient with metastatic pheochromocytoma. With appropriate preoperative measures, cement-augmented dorsal instrumentation represents a safe approach to stabilize vertebral bodies with metastatic malignant pheochromocytoma. Nevertheless, direct manipulation of metastatic lesions should be avoided as far as possible in order to minimize the risk of hemodynamic complications.

Metastases but not cardiovascular mortality reduces life expectancy following surgical resection of apparently benign pheochromocytoma.

Science.gov (United States)

Timmers, H J L M; Brouwers, F M; Hermus, A R M M; Sweep, F C G J; Verhofstad, A A J; Verbeek, A L M; Pacak, K; Lenders, J W M

2008-12-01

The treatment of choice for non-metastatic pheochromocytoma is surgical resection. Its goals are to abolish catecholamine hypersecretion, normalize blood pressure, and prevent further tumor growth or progression to metastatic disease. Data on long-term mortality and morbidity after pheochromocytoma surgery are limited. We here report a retrospective study on the long-term outcome after surgery for apparently benign pheochromocytoma at the Radboud University Nijmegen Medical Centre. Data on clinical presentation, treatment, post-surgical blood pressure and recurrence, metastasis and death were collected of 69 consecutive patients (January 1966-December 2000; follow-up: until death or January 2006). Survival was compared with survival of a matched reference population. Two patients died of surgical complications. All ten patients with metastatic disease (including three diagnosed at first surgery) died. At follow-up, 40 patients were alive and recurrence free and three patients were lost to follow up. Two patients experienced a benign recurrence. Mean+/-s.d. follow-up was 10.2+/-7.5 (median 9, range 1-38) years. Kaplan-Meier estimates for 5- and 10-year survival since surgery were 85.8% (95% CI: 77.2-94.4%) and 74.2% (95% CI: 62.0-86.4%) for patients versus 95.5 and 89.4% in the reference population (Prisk of developing metastatic disease. Only one-third becomes normotensive without antihypertensive medication. Therefore, lifelong follow-up is warranted.

Incidences of types of cancer in irradiated parabiont rats

International Nuclear Information System (INIS)

Warren, S.; Chute, R.N.; Brown, C.E.; Gates, O.

1982-01-01

A total body dose of 1000 R X radiation to 1252 male and 1366 female NEDH rats protected by permanent parabiosis to an untreated partner yielded respective cancer incidences of 42.7 and 38.3% within mean life-spans slightly less than single controls. These incidences were significant at the 1% level of probability compared with lower rates in shielded partners as well as in over 600 control parabiont partners and 700 single controls in which both sexes were nearly equally represented. Significant cancer incidences were induced in skin and islet cells of males, soft supporting tissue, renal tubules, bone of males and females, and ovary. Parabiosis per se provided local conditions conducive to the development of sarcomas, possibly enhanced by radiation, in anastomosed tissue as well as systemic changes promoting the spontaneous development of lymphoma and leukemia in females and inhibiting that of mammary carcinoma in females and malignant pheochromocytoma in males. The effects in females were largely canceled by radiation. The function of dose and its modification by factors contingent to parabiosis are discussed in relation to reported data on rats of other strains exposed to sublethal or lethal total-body X-ray doses

β-Cell dedifferentiation, reduced duct cell plasticity, and impaired β-cell mass regeneration in middle-aged rats.

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Téllez, Noèlia; Vilaseca, Marina; Martí, Yasmina; Pla, Arturo; Montanya, Eduard

2016-09-01

Limitations in β-cell regeneration potential in middle-aged animals could contribute to the increased risk to develop diabetes associated with aging. We investigated β-cell regeneration of middle-aged Wistar rats in response to two different regenerative stimuli: partial pancreatectomy (Px + V) and gastrin administration (Px + G). Pancreatic remnants were analyzed 3 and 14 days after surgery. β-Cell mass increased in young animals after Px and was further increased after gastrin treatment. In contrast, β-cell mass did not change after Px or after gastrin treatment in middle-aged rats. β-Cell replication and individual β-cell size were similarly increased after Px in young and middle-aged animals, and β-cell apoptosis was not modified. Nuclear immunolocalization of neurog3 or nkx6.1 in regenerative duct cells, markers of duct cell plasticity, was increased in young but not in middle-aged Px rats. The pancreatic progenitor-associated transcription factors neurog3 and sox9 were upregulated in islet β-cells of middle-aged rats and further increased after Px. The percentage of chromogranin A+/hormone islet cells was significantly increased in the pancreases of middle-aged Px rats. In summary, the potential for compensatory β-cell hyperplasia and hypertrophy was retained in middle-aged rats, but β-cell dedifferentiation and impaired duct cell plasticity limited β-cell regeneration. Copyright © 2016 the American Physiological Society.

Pheochromocytoma diagnosed after anticoagulation for atrial fibrillation ablation procedure: a giant in disguise.

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Galvão Braga, Carlos; Ribeiro, Sílvia; Martins, Juliana; Arantes, Carina; Ramos, Vítor; Primo, João; Magalhães, Sónia; Correia, Adelino

2014-04-01

Pheochromocytoma is a rare catecholamine-producing tumor, discovered incidentally in 50% of cases. We present the case of a 44-year-old male with a history of paroxysmal palpitations. Baseline ECG, transthoracic echocardiogram and ECG stress test showed no relevant alterations. Paroxysmal atrial fibrillation was detected on 24-hour Holter ECG. After antiarrhythmic therapy, the patient remained symptomatic, and was accordingly referred for electrophysiological study and atrial fibrillation ablation. Anticoagulation was initiated before the procedure. After ablation and still anticoagulated, he complained of hematospermia. The abdominal and pelvic imaging study showed a 10-cm left adrenal mass, predominantly cystic, compatible with pheochromocytoma, which was confirmed after biochemical tests (increased urine metanephrines and plasma catecholamines). Metaiodobenzylguanidine scintigraphy scanning confirmed localized disease in the adrenal gland, excluding other uptake foci. Following appropriate preoperative management, surgical resection of the giant mass was performed successfully and without complications. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Demonstration of immunochemical identity between the nerve growth factor-inducible large external (NILE) glycoprotein and the cell adhesion molecule L1

DEFF Research Database (Denmark)

Bock, E; Richter-Landsberg, C; Faissner, A

1985-01-01

The nerve growth factor-inducible large external (NILE) glycoprotein and the neural cell adhesion molecule L1 were shown to be immunochemically identical. Immunoprecipitation with L1 and NILE antibodies of [3H]fucose-labeled material from culture supernatants and detergent extracts of NGF......-treated rat PC12 pheochromocytoma cells yielded comigrating bands by SDS-PAGE. NILE antibodies reacted with immunopurified L1 antigen, but not with N-CAM and other L2 epitope-bearing glycoproteins from adult mouse brain. Finally, by sequential immunoprecipitation from detergent extracts of [35S......]methionine-labeled early post-natal cerebellar cell cultures or [3H]fucose-labeled NGF-treated PC12 cells, all immunoreactivity for NILE antibody could be removed by pre-clearing with L1 antibody and vice versa....

Kupffer cell blockade prevents rejection of human insulinoma cell xenograft in rats

International Nuclear Information System (INIS)

Lazar, G. Jr.; Farkas, G.; Lazar, G.

1998-01-01

Alloantigens are recognized by T-cells in the context of both class I and class II antigen, but class II antigens predominate in the recognition of xenoantigens. Since class II molecules bind peptides derived from exogenous proteins that have been phagocytized and digested into small fragments by antigen presenting cells, in the present studies the effect of gadolinium chloride (GdCl 3 )-induced Kupffer cell blockade on the survival of discordant insulinoma cell xenografts was investigated. Insulinoma cells isolated by means of collagenase from human insulinoma and cultured were transplanted through the v. portae into the liver of streptozotocin-induced diabetic, male, CFY inbred rats. In the control, streptozotocin-treated rats, the decrease in blood glucose level was only transitory, in contrast with the GdCl 3 -pretreated diabetic rats, which remained normoglycaemic during the 2-week observation period. Histologically, in the liver and lung of rats pre-treated with GdCl 3 , large areas of extensively proliferating insulinoma cells were seen, whereas no insulinoma cells were seen in either the liver or the lung of diabetic-control rats, not-treated with GdCl 3 . These studies suggest that the Kupffer cells play significant roles in the recognition of xenoantigens and the induction of xenograft rejection. (orig.)

Subretinally transplanted embryonic stem cells rescue photoreceptor cells from degeneration in the RCS rats.

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Schraermeyer, U; Thumann, G; Luther, T; Kociok, N; Armhold, S; Kruttwig, K; Andressen, C; Addicks, K; Bartz-Schmidt, K U

2001-01-01

The Royal College of Surgeons (RCS) rat is an animal model for retinal degeneration such as the age-related macular degeneration. The RCS rat undergoes a progressive retinal degeneration during the early postnatal period. A potential treatment to prevent this retinal degeneration is the transplantation into the subretinal space of cells that would replace functions of the degenerating retinal pigment epithelium (RPE) cells or may form neurotrophic factors. In this study we have investigated the potential of subretinally transplanted embryonic stem cells to prevent the genetically determined photoreceptor cell degeneration in the RCS rat. Embryonic stem cells from the inner cell mass of the mouse blastocyst were allowed to differentiate to neural precursor cells in vitro and were then transplanted into the subretinal space of 20-day-old RCS rats. Transplanted and sham-operated rats were sacrificed 2 months following cell transplantation. The eyes were enucleated and photoreceptor degeneration was quantified by analyzing and determining the thickness of the outer nuclear layer by light and electron microscopy. In the eyes transplanted with embryonic cells up to 8 rows of photoreceptor cell nuclei were observed, whereas in nontreated control eyes the outer nuclear layer had degenerated completely. Transplantation of embryonic stem cells appears to delay photoreceptor cell degeneration in RCS rats.

Parathyroid hormone dependent T cell proliferation in uremic rats

DEFF Research Database (Denmark)

Lewin, E; Ladefoged, Jens; Brandi, L

1993-01-01

Chronic renal failure (CRF) is combined with an impairment of the immune system. The T cell may be a target for the action of parathyroid hormone (PTH). Rats with CRF have high blood levels of PTH. Therefore, the present investigation examined some aspects of the T cell function in both normal...... and CRF rats before and after parathyroidectomy and after an isogenic kidney transplantation. The T cell proliferative response to phytohemagglutinin (PHA) stimulation was significantly higher in peripheral blood mononuclear cell (PBMC) cultures obtained from CRF rats than from normal rats. After...... parathyroidectomy the T cells of normal as well as of uremic rats could still be significantly stimulated by PHA, but now no significant difference was seen. When CRF was reversed after an isogenic kidney transplantation and PTH reversed to levels in the normal range, the T cell proliferative response to PHA...

Usefulness of [18F]-DA and [18F]-DOPA for PET imaging in a mouse model of pheochromocytoma

International Nuclear Information System (INIS)

Martiniova, Lucia; Cleary, Susannah; Lai, Edwin W.; Kiesewetter, Dale O.; Seidel, Jurgen; Dawson, Linda F.; Phillips, Jacqueline K.; Thomasson, David; Chen Xiaoyuan; Eisenhofer, Graeme; Powers, James F.; Kvetnansky, Richard

2012-01-01

Purpose: To evaluate the usefulness of [ 18 F]-6-fluorodopamine ([ 18 F]-DA) and [ 18 F]-L-6-fluoro-3,4-dihydroxyphenylalanine ([ 18 F]-DOPA) positron emission tomography (PET) in the detection of subcutaneous (s.c.) and metastatic pheochromocytoma in mice; to assess the expression of the norepinephrine transporter (NET) and vesicular monoamine transporters 1 and 2 (VMAT1 and VMAT2), all important for [ 18 F]-DA and [ 18 F]-DOPA uptake. Furthermore, to compare tumor detection by micro-computed tomography (microCT) to magnetic resonance imaging (MRI) in individual mouse. Methods: SUV max values were calculated from [ 18 F]-DA and [ 18 F]-DOPA PET, tumor-to-liver ratios (TLR) were obtained and expression of NET, VMAT1 and VMAT2 was evaluated. Results: [ 18 F]-DA detected less metastatic lesions compared to [ 18 F]-DOPA. TLR values for liver metastases were 2.26–2.71 for [ 18 F]-DOPA and 1.83–2.83 for [ 18 F]-DA. A limited uptake of [ 18 F]-DA was found in s.c. tumors (TLR=0.22-0.27) compared to [ 18 F]-DOPA (TLR=1.56-2.24). Overall, NET and VMAT2 were expressed in all organ and s.c. tumors. However, s.c. tumors lacked expression of VMAT1. We confirmed [ 18 F]-DA's high affinity for the NET for its uptake and VMAT1 and VMAT2 for its storage and retention in pheochromocytoma cell vesicles. In contrast, [ 18 F]-DOPA was found to utilize only VMAT2. Conclusion: MRI was superior in the detection of all organ tumors compared to microCT and PET. [ 18 F]-DOPA had overall better sensitivity than [ 18 F]-DA for the detection of metastases. Subcutaneous tumors were localized only with [ 18 F]-DOPA, a finding that may reflect differences in expression of VMAT1 and VMAT2, perhaps similar to some patients with pheochromocytoma where [ 18 F]-DOPA provides better visualization of lesions than [ 18 F]-DA.

Protective Effect of Quercetin against Oxidative Stress-Induced Cytotoxicity in Rat Pheochromocytoma (PC-12) Cells.

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Bao, Dengke; Wang, Jingkai; Pang, Xiaobin; Liu, Hongliang

2017-07-06

Oxidative stress has been implicated in the pathogenesis of many kinds of neurodegenerative disorders, particularly Parkinson's disease. Quercetin is a bioflavonoid found ubiquitously in fruits and vegetables, and has antioxidative activity. However, the underlying mechanism of the antioxidative effect of quercetin in neurodegenerative diseases has not been well explored. Here, we investigated the antioxidative effect and underlying molecular mechanisms of quercetin on PC-12 cells. We found that PC-12 cells pretreated with quercetin exhibited an increased cell viability and reduced lactate dehydrogenase (LDH) release when exposed to hydrogen peroxide (H₂O₂). The significantly-alleviated intracellular reactive oxygen species (ROS), malondialdehyde (MDA), and lipoperoxidation of the cell membrane of PC-12 cells induced by H₂O₂ were observed in the quercetin pretreated group. Furthermore, quercetin pretreatment markedly reduced the apoptosis of PC-12 cells and hippocampal neurons. The inductions of antioxidant enzyme catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) in PC-12 cells exposed to H₂O₂ were significantly reduced by preatment with quercetin. In addition, quercetin pretreatment significantly increased Bcl-2 expression, and reduced Bax, cleaved caspase-3 and p53 expressions. In conclusion, this study demonstrated that quercetin exhibited a protective effect against oxidative stress-induced apoptosis in PC-12 cells. Our findings suggested that quercetin may be developed as a novel therapeutic agent for neurodegenerative diseases induced by oxidative stress.

Generation and characterization of rat liver stem cell lines and their engraftment in a rat model of liver failure

Science.gov (United States)

Kuijk, Ewart W.; Rasmussen, Shauna; Blokzijl, Francis; Huch, Meritxell; Gehart, Helmuth; Toonen, Pim; Begthel, Harry; Clevers, Hans; Geurts, Aron M.; Cuppen, Edwin

2016-01-01

The rat is an important model for liver regeneration. However, there is no in vitro culture system that can capture the massive proliferation that can be observed after partial hepatectomy in rats. We here describe the generation of rat liver stem cell lines. Rat liver stem cells, which grow as cystic organoids, were characterized by high expression of the stem cell marker Lgr5, by the expression of liver progenitor and duct markers, and by low expression of hepatocyte markers, oval cell markers, and stellate cell markers. Prolonged cultures of rat liver organoids depended on high levels of WNT-signalling and the inhibition of BMP-signaling. Upon transplantation of clonal lines to a Fah−/− Il2rg−/− rat model of liver failure, the rat liver stem cells engrafted into the host liver where they differentiated into areas with FAH and Albumin positive hepatocytes. Rat liver stem cell lines hold potential as consistent reliable cell sources for pharmacological, toxicological or metabolic studies. In addition, rat liver stem cell lines may contribute to the development of regenerative medicine in liver disease. To our knowledge, the here described liver stem cell lines represent the first organoid culture system in the rat. PMID:26915950

Protective Effect of Quercetin against Oxidative Stress-Induced Cytotoxicity in Rat Pheochromocytoma (PC-12 Cells

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Dengke Bao

2017-07-01

Full Text Available Oxidative stress has been implicated in the pathogenesis of many kinds of neurodegenerative disorders, particularly Parkinson’s disease. Quercetin is a bioflavonoid found ubiquitously in fruits and vegetables, and has antioxidative activity. However, the underlying mechanism of the antioxidative effect of quercetin in neurodegenerative diseases has not been well explored. Here, we investigated the antioxidative effect and underlying molecular mechanisms of quercetin on PC-12 cells. We found that PC-12 cells pretreated with quercetin exhibited an increased cell viability and reduced lactate dehydrogenase (LDH release when exposed to hydrogen peroxide (H2O2. The significantly-alleviated intracellular reactive oxygen species (ROS, malondialdehyde (MDA, and lipoperoxidation of the cell membrane of PC-12 cells induced by H2O2 were observed in the quercetin pretreated group. Furthermore, quercetin pretreatment markedly reduced the apoptosis of PC-12 cells and hippocampal neurons. The inductions of antioxidant enzyme catalase (CAT, superoxide dismutase (SOD, and glutathione peroxidase (GSH-Px in PC-12 cells exposed to H2O2 were significantly reduced by preatment with quercetin. In addition, quercetin pretreatment significantly increased Bcl-2 expression, and reduced Bax, cleaved caspase-3 and p53 expressions. In conclusion, this study demonstrated that quercetin exhibited a protective effect against oxidative stress-induced apoptosis in PC-12 cells. Our findings suggested that quercetin may be developed as a novel therapeutic agent for neurodegenerative diseases induced by oxidative stress.

Miocardiopatía dilatada y feocromocitoma Dilated myocardiopathy and pheochromocytoma

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José Luis González González

2013-03-01

Full Text Available El feocromocitoma, un tumor de baja incidencia con un comportamiento benigno en la mayoría de los casos, puede ser el responsable de extensas manifestaciones cardiovasculares.Las manifestaciones sobre el miocardio pueden ser de profundas consecuencias, pues llegan a producir una miocardiopatía dilatada con insuficiencia cardiaca severa. La exéresis del tumor suele ser curativa en el 90 % de los casos y el manejo perioperatorio muy complejo. Se presenta un paciente joven portador de un feocromocitoma , que sometido a la larga acción de las catecolaminas llegó a desarrollar una miocardiopatía dilatada con criterio de trasplante cardiaco. La cirugía adrenal fue curativa en nuestro paciente.Pheochromocytoma, a low incidence tumor of benign behavior in most of cases, can cause extensive cardiovascular manifestations. These manifestations on the myocardium can have deep consequences since they may lead to dilated myocardiopathy with severe heart failure. The excision of tumor may be the curative solution for 90 % of cases but the perioperative management is very complex. This is the case of a young patient who carries pheochromocytoma and after a long-acting catecholemine-based treatment, he developed dilated myocardiopathy, and the medical criterion was that he required heart transplantation. The adrenal surgery was successfully healing in our patient.

Unilateral and Bilateral Adrenalectomy for Pheochromocytoma Requires Adjustment of Urinary and Plasma Metanephrine Reference Ranges

NARCIS (Netherlands)

Osinga, Thamara E.; van den Eijnden, Maartje H. A.; Kema, Ido P.; Kerstens, Michiel N.; Dullaart, Robin P. F.; de Jong, Wilhelmina H. A.; Sluiter, Wim J.; Links, Thera P.; van der Horst-Schrivers, Anouk N. A.

Context: Follow-up after adrenalectomy for pheochromocytoma is recommended because of a recurrence risk. During follow-up, plasma and/or urinary metanephrine (MN) and normetanephrine (NMN) are interpreted using reference ranges obtained in healthy subjects. Objective: Because adrenalectomy may

Epidermal growth factor prevents thallium(I)- and thallium(III)-mediated rat pheochromocytoma (PC12) cell apoptosis.

Science.gov (United States)

Pino, María Teresa Luján; Marotte, Clarisa; Verstraeten, Sandra Viviana

2017-03-01

We have reported recently that the proliferation of PC12 cells exposed to micromolar concentrations of Tl(I) or Tl(III) has different outcomes, depending on the absence (EGF - cells) or the presence (EGF + cells) of epidermal growth factor (EGF) added to the media. In the current work, we investigated whether EGF supplementation could also modulate the extent of Tl(I)- or Tl(III)-induced cell apoptosis. Tl(I) and Tl(III) (25-100 μM) decreased cell viability in EGF - but not in EGF + cells. In EGF - cells, Tl(I) decreased mitochondrial potential, enhanced H 2 O 2 generation, and activated mitochondrial-dependent apoptosis. In addition, Tl(III) increased nitric oxide production and caused a misbalance between the anti- and pro-apoptotic members of Bcl-2 family. Tl(I) increased ERK1/2, JNK, p38, and p53 phosphorylation in EGF - cells. In these cells, Tl(III) did not affect ERK1/2 and JNK phosphorylation but increased p53 phosphorylation that was related to the promotion of cell senescence. In addition, this cation significantly activated p38 in both EGF - and EGF + cells. The specific inhibition of ERK1/2, JNK, p38, or p53 abolished Tl(I)-mediated EGF - cell apoptosis. Only when p38 activity was inhibited, Tl(III)-mediated apoptosis was prevented in EGF - and EGF + cells. Together, current results indicate that EGF partially prevents the noxious effects of Tl by preventing the sustained activation of MAPKs signaling cascade that lead cells to apoptosis and point to p38 as a key mediator of Tl(III)-induced PC12 cell apoptosis.

Krebs cycle metabolite profiling for identification and stratification of pheochromocytomas/paragangliomas due to succinate dehydrogenase deficiency

NARCIS (Netherlands)

Richter, S; Peitzsch, M.; Rapizzi, E.; Lenders, J.W.M.; Qin, N.; Cubas, A.A. de; Schiavi, F.; Rao, J.U.; Beuschlein, F.; Quinkler, M.; Timmers, H.J.L.M.; Opocher, G.; Mannelli, M.; Pacak, K.; Robledo, M.; Eisenhofer, G.

2014-01-01

CONTEXT: Mutations of succinate dehydrogenase A/B/C/D genes (SDHx) increase susceptibility to development of pheochromocytomas and paragangliomas (PPGLs), with particularly high rates of malignancy associated with SDHB mutations. OBJECTIVE: We assessed whether altered succinate dehydrogenase

T-cell proliferative responses following sepsis in neonatal rats.

Science.gov (United States)

Dallal, Ousama; Ravindranath, Thyyar M; Choudhry, Mashkoor A; Kohn, Annamarie; Muraskas, Jonathan K; Namak, Shahla Y; Alattar, Mohammad H; Sayeed, Mohammed M

2003-01-01

Both experimental and clinical evidence suggest a suppression of T-cell function in burn and sepsis. The objective of the present study was to evaluate splenocyte and purified T-cell proliferative response and IL-2 production in septic neonatal rats. We also examined if alterations in T-cell proliferation and IL-2 production in neonatal sepsis is due to elevation in PGE2. PGE2 is known to play a significant role in T-cell suppression during sepsis in adults. Sepsis was induced in 15-day-old neonatal Sprague-Dawley rats by implanting 0.1 cm3 of fecal pellet impregnated with Escherichia coli (50 CFU) and Bacteroides fragilis (10(3) CFU). Animals receiving fecal pellets without the bacteria were designated as sterile. A group of septic and sterile rats were treated with PGE2 synthesis inhibitors, NS398 and resveratrol. These treatments of animals allowed us to evaluate the role of PGE2 in T-cell suppression during neonatal sepsis. Splenocytes as well as purified T cells were prepared and then proliferative response and IL-2 productive capacities were measured. A significant suppression of splenocyte proliferation and IL-2 production was noticed in both sterile and septic animals compared to the T cells from unoperated control rats. In contrast, the proliferation and IL-2 production by nylon wool purified T cells in sterile rats was not significantly different from control rats, whereas, a significant suppression in Con A-mediated T-cell proliferation and IL-2 production noticed in septic rat T cells compared to the sterile and control rat T cells. Such decrease in T-cell proliferation and IL-2 production was accompanied with 20-25% deaths in neonates implanted with septic pellets. No mortality was noted in sterile-implanted neonates. Treatment of animals with COX-1 inhibitor had no effect on T-cell proliferation response in both septic and sterile groups, whereas COX-2 inhibitor abrogated the decrease in T-cell proliferative response in the septic group. The treatment

Neurite outgrowth stimulatory effects of myco­synthesized AuNPs from Hericium erinaceus (Bull.: Fr. Pers. on pheochromocytoma (PC-12 cells

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Raman J

2015-09-01

Full Text Available Jegadeesh Raman,1 Hariprasath Lakshmanan,1 Priscilla A John,1,2 Chan Zhijian,3 Vengadesh Periasamy,3 Pamela David,1,4 Murali Naidu,1,4 Vikineswary Sabaratnam1,2 1Mushroom Research Centre, 2Institute of Biological Sciences, Faculty of Science, University of Malaya, 3Low Dimensional Materials Research Center (LDMRC, Department of Physics, Faculty of Science, 4Department of Anatomy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia Background: Hericium erinaceus has been reported to have a wide range of medicinal properties such as stimulation of neurite outgrowth, promotion of functional recovery of axonotmetic peroneal nerve injury, antioxidant, antihypertensive, and antidiabetic properties. In recent years, the green synthesis of gold nanoparticles (AuNPs has attracted intense interest due to the potential use in biomedical applications. The aim of this study was to investigate the effects of AuNPs from aqueous extract of H. erinaceus on neurite outgrowth of rat pheochromocytoma (PC-12 cells. Methods: The formation of AuNPs was characterized by UV–visible spectrum, energy dispersive X-ray (EDX, field-emission scanning electron microscope (FESEM, transmission electron microscopy (TEM, particle size distribution, and Fourier transform-infrared spectroscopy (FTIR. Furthermore, the neurite extension study of synthesized AuNPs was evaluated by in vitro assay. Results: The AuNPs exhibited maximum absorbance between 510 and 600 nm in UV–visible spectrum. FESEM and TEM images showed the existence of nanoparticles with sizes of 20–40 nm. FTIR measurements were carried out to identify the possible biomolecules responsible for capping and efficient stabilization of the nanoparticles. The purity and the crystalline properties were confirmed by EDX diffraction analysis, which showed strong signals with energy peaks in the range of 2–2.4 keV, indicating the existence of gold atoms. The synthesized AuNPs showed significant neurite

Numeric and volumetric changes in Leydig cells during aging of rats.

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Neves, Bruno Vinicius Duarte; Lorenzini, Fernando; Veronez, Djanira; Miranda, Eduardo Pereira de; Neves, Gabriela Duarte; Fraga, Rogério de

2017-10-01

To analyze the effects of aging in rats on the nuclear volume, cytoplasmic volume, and total volume of Leydig cells, as well as their number. Seventy-two Wistar rats were divided into six subgroups of 12 rats, which underwent right orchiectomy at 3, 6, 9, 12, 18, and 24 months of age. The weight and volume of the resected testicles were assessed. A stereological study of Leydig cells was conducted, which included measurements of cell number and nuclear, cytoplasmic, and total cell volumes. The weight and volume of the resected testicles showed reductions with age. Only the subgroup composed of 24-month old rats showed a decrease in the nuclear volume of Leydig cells. Significant reductions in the cytoplasmic volume and total volume of Leydig cells were observed in 18- and 24-month old rats. The number of Leydig cells did not vary significantly with age. Aging in rats resulted in reduction of the nuclear, cytoplasmic, and total cell volumes of Leydig cells. There was no change in the total number of these cells during aging.

Transplantation of rat embryonic stem cell-derived retinal progenitor cells preserves the retinal structure and function in rat retinal degeneration.

Science.gov (United States)

Qu, Zepeng; Guan, Yuan; Cui, Lu; Song, Jian; Gu, Junjie; Zhao, Hanzhi; Xu, Lei; Lu, Lixia; Jin, Ying; Xu, Guo-Tong

2015-11-09

Degenerative retinal diseases like age-related macular degeneration (AMD) are the leading cause of blindness. Cell transplantation showed promising therapeutic effect for such diseases, and embryonic stem cell (ESC) is one of the sources of such donor cells. Here, we aimed to generate retinal progenitor cells (RPCs) from rat ESCs (rESCs) and to test their therapeutic effects in rat model. The rESCs (DA8-16) were cultured in N2B27 medium with 2i, and differentiated to two types of RPCs following the SFEBq method with modifications. For rESC-RPC1, the cells were switched to adherent culture at D10, while for rESC-RPC2, the suspension culture was maintained to D14. Both RPCs were harvested at D16. Primary RPCs were obtained from P1 SD rats, and some of them were labeled with EGFP by infection with lentivirus. To generate Rax::EGFP knock-in rESC lines, TALENs were engineered to facilitate homologous recombination in rESCs, which were cotransfected with the targeting vector and TALEN vectors. The differentiated cells were analyzed with live image, immunofluorescence staining, flow cytometric analysis, gene expression microarray, etc. RCS rats were used to mimic the degeneration of retina and test the therapeutic effects of subretinally transplanted donor cells. The structure and function of retina were examined. We established two protocols through which two types of rESC-derived RPCs were obtained and both contained committed retina lineage cells and some neural progenitor cells (NPCs). These rESC-derived RPCs survived in the host retinas of RCS rats and protected the retinal structure and function in early stage following the transplantation. However, the glia enriched rESC-RPC1 obtained through early and longer adherent culture only increased the b-wave amplitude at 4 weeks, while the longer suspension culture gave rise to evidently neuronal differentiation in rESC-RPC2 which significantly improved the visual function of RCS rats. We have successfully differentiated

Anesthesia for combined cesarean section and pheochromocytoma resection

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Sadhana Kulkarni

2017-01-01

Full Text Available Pheochromocytoma (PCC is a rare cause of hypertension during pregnancy [1:54000 pregnancies]. Fetomaternal morbidity and mortality is about 58% if the diagnosis is missed. Administration of anesthesia to patients with PCC is challenging. Associated pregnancy adds to the problems. This is a case report of a patient having PCC diagnosed at 26 weeks of gestation. With medical management pregnancy was continued till 34 weeks. She was posted for cesarean section and resection of PCC. Patient underwent surgery lasting for 7 h due to inferior vena cava tear and had stormy intra as well as postoperative course. Mother and baby had uneventful recovery due to continuous invasive monitoring and a good teamwork, despite limited anesthetic resources.

HIV-1 transgenic rats develop T cell abnormalities

International Nuclear Information System (INIS)

Reid, William; Abdelwahab, Sayed; Sadowska, Mariola; Huso, David; Neal, Ashley; Ahearn, Aaron; Bryant, Joseph; Gallo, Robert C.; Lewis, George K.; Reitz, Marvin

2004-01-01

HIV-1 infection leads to impaired antigen-specific T cell proliferation, increased susceptibility of T cells to apoptosis, progressive impairment of T-helper 1 (Th1) responses, and altered maturation of HIV-1-specific memory cells. We have identified similar impairments in HIV-1 transgenic (Tg) rats. Tg rats developed an absolute reduction in CD4 + and CD8 + T cells able to produce IFN-γ following activation and an increased susceptibility of T cells to activation-induced apoptosis. CD4 + and CD8 + effector/memory (CD45RC - CD62L - ) pools were significantly smaller in Tg rats compared to non-Tg controls, although the converse was true for the naieve (CD45RC + CD62L + ) T cell pool. Our interpretation is that the HIV transgene causes defects in the development of T cell effector function and generation of specific effector/memory T cell subsets, and that activation-induced apoptosis may be an essential factor in this process

Internalization and cellular pools of never growth factor in pheochromocytoma (PC12) cells

International Nuclear Information System (INIS)

Neet, K.E.; Kasaian, M.

1987-01-01

Nerve Growth Factor (NGF) binds to a cell surface receptor on responsive neuronal cells to initiate cell maintenance and/or differentiation regimes. The purpose of these studies was to define quantitatively the fate of NGF in PC12 cells with respect to various cellular compartments in a single series of biochemical experiments. Different binding methodologies were evaluated in suspension and on plates. 50 pM 125 I-NGF was bound to rat PC12 cells in suspension for 30 min at 37 0 , followed by various methods and combinations of methods to remove subsets of bound ligand. Distinction could be made between NGF bound to fast vs. slow cell surface receptors, NGF bound to slow receptors at the cell surface vs. cell interior, and detergent-soluble vs. cytoskeletally-attached NGF. These treatments defined the relative size of five pools, including the fast receptor (65%), two intracellular compartments (12% and 3%) susceptible to nonionic detergent, and a detergent-stable intracellular pool of ligand (16%). At 37 0 the cold chase stable and the acid stable pools were about the same size because of rapid internalization, but the slow receptor was measurable at 4 0 . Inhibitors were used to define the route of NGF through the cell from the plasma membrane to degradation. Chloroquine caused accumulation of NGF only in pools that were not associated with the cytoskeleton, implicating this compartment in supplying ligand to the lysosome. Results with cytochalasin B and colchicine and suggested both microfilament and microtubule pathways in NGF degradation. A model for the movement of NGF through the cell was developed based on these observations

Edaravone combined with Schwann cell transplantation may repair spinal cord injury in rats

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Shu-quan Zhang

2015-01-01

Full Text Available Edaravone has been shown to delay neuronal apoptosis, thereby improving nerve function and the microenvironment after spinal cord injury. Edaravone can provide a favorable environment for the treatment of spinal cord injury using Schwann cell transplantation. This study used rat models of complete spinal cord transection at T 9. Six hours later, Schwann cells were transplanted in the head and tail ends of the injury site. Simultaneously, edaravone was injected through the caudal vein. Eight weeks later, the PKH-26-labeled Schwann cells had survived and migrated to the center of the spinal cord injury region in rats after combined treatment with edaravone and Schwann cells. Moreover, the number of PKH-26-labeled Schwann cells in the rat spinal cord was more than that in rats undergoing Schwann cell transplantation alone or rats without any treatment. Horseradish peroxidase retrograde tracing revealed that the number of horseradish peroxidase-positive nerve fibers was greater in rats treated with edaravone combined withSchwann cells than in rats with Schwann cell transplantation alone. The results demonstrated that lower extremity motor function and neurophysiological function were better in rats treated with edaravone and Schwann cells than in rats with Schwann cell transplantation only. These data confirmed that Schwann cell transplantation combined with edaravone injection promoted the regeneration of nerve fibers of rats with spinal cord injury and improved neurological function.

Incidental finding of pheochromocytoma after imaging exam

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Bianca Lara Teixeira

2017-11-01

Full Text Available Pheochromocytomas — 90% of those being benign — are relatively rare tumors of the adrenal medulla, catecholamines producers. About 75% of patients manifest the sudden classic triad characterized by severe hypertension, palpitations and headache. The diagnosis is confirmed by urinary metanephrines dosage, and radiological tests such as ultrasonography, computed tomography and magnetic resonance imaging. The curative treatment consists in removing the tumor, and videolaparoscopy is the chosen surgical technique. This report describes the case of a woman, who sought the emergency unit complaining of left back, and after imaging tests, was evidenced a large adrenal mass. The patient presented as a symptom linked to the secreting tumor was only secondary hypertension. It was opted to perform an open surgery as a consequence of the tumor dimensions, and the person presents herself normotensive after left adrenectomy.

Comparison of the 68Ga-DOTATATA PET/CT, FDG PET/CT, and MIBG SPECT/CT in the Evaluation of Suspected Primary Pheochromocytomas and Paragangliomas.

Science.gov (United States)

Jing, Hongli; Li, Fang; Wang, Ling; Wang, Zhenghua; Li, Wei; Huo, Li; Zhang, Jingjing

2017-07-01

Anatomical imaging modalities including CT and MRI are the mainstay of evaluation of primary pheochromocytoma or paraganglioma. However, nuclear medicine imaging is frequently necessary to determine the nature of the lesions. The purpose of this investigation is to assess which commonly used nuclear medicine modality might have a better diagnostic value in this clinical setting. Eight patients who had been suspected of having either primary pheochromocytoma or primary paraganglioma and 1 patient with known pheochromocytoma were included in the analysis. Among the 8 patients without known diagnosis, 7 had been suggested by anatomical imaging modalities, whereas one of them presented with initial negative anatomical imaging interpretation. All of 9 patients underwent Ga-DOTATATA PET/CT, FDG PET/CT, and MIBG SPECT/CT for further evaluation. The imaging findings were compared with postsurgical pathology and follow-up. Both Ga-DOTATATA PET/CT and MIBG SPECT/CT accurately identified 9 primary tumors, whereas FDG PET/CT showed increased activity in 8 of 9 primary tumors. Both Ga-DOTATATA and FDG PET/CT are able to detect associated extra-adrenal lesions not shown on MIBG study in patients with multiple endocrine neoplasia syndrome. Ga-DOTATATA PET/CT could be the nuclear medicine imaging choice to evaluate suspected primary pheochromocytoma or paraganglioma, especially in the situation of multiple endocrine neoplasia syndrome.

Cancer of rat ovaries: Sertoli cell or granulosa-theca cell tumours

International Nuclear Information System (INIS)

Knowles, J.F.

1983-01-01

The effects of X-radiation (0-1.25 Gy) given 24 hours after neonatal injections of the carcinogen ethyl nitrosourea (ENU) (0-10 mg/kg) in female rats were studied. Twelve out of 118 rats bore single ovarian tumours. A substantial excess of ovarian tumours occurred in the rats given 4 mg/kg ENU and 1.25 GY X-rays but not in others given ENU alone, radiation alone or 10 mg/kg ENU and 1.25 Gy. The tumours were all found in old rats (657-1085 days). In all of the tumours the presence of tubular formations suggested a diagnosis of ovarian Sertoli cell tumour. In two tumours, only a few tubular structures were seen and fibrous stromal tissue predominated, suggesting a diagnosis of granulosa-theca cell tumour. All other tumours were a mixture of both elements. (U.K.)

Establishment of cell lines with rat spermatogonial stem cell characteristics

NARCIS (Netherlands)

van Pelt, Ans M. M.; Roepers-Gajadien, Hermien L.; Gademan, Iris S.; Creemers, Laura B.; de Rooij, Dirk G.; van Dissel-Emiliani, Federica M. F.

2002-01-01

Spermatogonial cell lines were established by transfecting a mixed population of purified rat A(s) (stem cells), A(pr) and A(al) spermatogonia with SV40 large T antigen. Two cell lines were characterized and found to express Hsp90alpha and oct-4, specific markers for germ cells and A spermatogonia,

Warburg effect's manifestation in aggressive pheochromocytomas and paragangliomas: insights from a mouse cell model applied to human tumor tissue.

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Stephanie M J Fliedner

Full Text Available A glycolytic profile unifies a group of pheochromocytomas and paragangliomas (PHEOs/PGLs with distinct underlying gene defects, including von Hippel-Lindau (VHL and succinate dehydrogenase B (SDHB mutations. Nevertheless, their tumor aggressiveness is distinct: PHEOs/PGLs metastasize rarely in VHL-, but frequently in SDHB-patients. To date, the molecular mechanisms causing the more aggressive phenotype in SDHB-PHEOs/PGLs remain largely unknown. Recently, however, an excellent model to study aggressive PHEOs (mouse tumor tissue (MTT cells has been developed from mouse PHEO cells (MPC. We employed this model for a proteomics based approach to identify changes characteristic for tumor aggressiveness, which we then explored in a homogeneous set of human SDHB- and VHL-PHEOs/PGLs. The increase of glucose transporter 1 in VHL, and of hexokinase 2 in VHL and SDHB, confirmed their glycolytic profile. In agreement with the cell model and in support of decoupling of glycolysis, the Krebs cycle and oxidative phosphorylation (OXPHOS, SDHB tumors showed increased lactate dehydrogenase levels. In SDHB-PGLs OXPHOS complex activity was increased at complex III and, as expected, decreased at complex II. Moreover, protein and mRNA expression of all tested OXPHOS-related genes were higher in SDHB- than in VHL-derived tumors. Although there was no direct evidence for increased reactive oxygen species production, elevated superoxide dismutase 2 expression may reflect elevated oxidative stress in SDHB-derived PHEOs/PGLs. For the first time, we show that despite dysfunction in complex II and evidence for a glycolytic phenotype, the Warburg effect does not seem to fully apply to SDHB-PHEOs/PGLs with respect to decreased OXPHOS. In addition, we present evidence for increased LDHA and SOD2 expression in SDHB-PHEOs/PGLs, proteins that have been proposed as promising therapeutic targets in other cancers. This study provides new insight into pathogenic mechanisms in

Differentiation ability of rat postnatal dental pulp cells in vitro.

NARCIS (Netherlands)

Zhang, W.; Walboomers, X.F.; Wolke, J.G.C.; Bian, Z.; Fan, M.W.; Jansen, J.A.

2005-01-01

The current rapid progression in stem cell research has enhanced our knowledge of dental tissue regeneration. In this study, rat dental pulp cells were isolated and their differentiation ability was evaluated. First, dental pulp cells were obtained from maxillary incisors of male Wistar rats.

PPARα agonists up-regulate organic cation transporters in rat liver cells

International Nuclear Information System (INIS)

Luci, Sebastian; Geissler, Stefanie; Koenig, Bettina; Koch, Alexander; Stangl, Gabriele I.; Hirche, Frank; Eder, Klaus

2006-01-01

It has been shown that clofibrate treatment increases the carnitine concentration in the liver of rats. However, the molecular mechanism is still unknown. In this study, we observed for the first time that treatment of rats with the peroxisome proliferator activated receptor (PPAR)-α agonist clofibrate increases hepatic mRNA concentrations of organic cation transporters (OCTNs)-1 and -2 which act as transporters of carnitine into the cell. In rat hepatoma (Fao) cells, treatment with WY-14,643 also increased the mRNA concentration of OCTN-2. mRNA concentrations of enzymes involved in carnitine biosynthesis were not altered by treatment with the PPARα agonists in livers of rats and in Fao cells. We conclude that PPARα agonists increase carnitine concentrations in livers of rats and cells by an increased uptake of carnitine into the cell but not by an increased carnitine biosynthesis

Turnover time of Leydig cells and other interstitial cells in testes of adult rats

NARCIS (Netherlands)

Teerds, K. J.; de rooij, D. G.; Rommerts, F. F.; van der Tweel, I.; Wensing, C. J.

1989-01-01

The aim of this study was to investigate the turnover of Leydig cells and other interstitial cells in the adult rat testis. Normal adult rats received injections of [3H]thymidine at 9:00 and 21:00 for 2, 5, or 8 days. The percentage of labeled Leydig cells, which was initially low (0.8% +/- 0.2%),

Combination cell therapy with mesenchymal stem cells and neural stem cells for brain stroke in rats.

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Hosseini, Seyed Mojtaba; Farahmandnia, Mohammad; Razi, Zahra; Delavari, Somayeh; Shakibajahromi, Benafsheh; Sarvestani, Fatemeh Sabet; Kazemi, Sepehr; Semsar, Maryam

2015-05-01

Brain stroke is the second most important events that lead to disability and morbidity these days. Although, stroke is important, there is no treatment for curing this problem. Nowadays, cell therapy has opened a new window for treating central nervous system disease. In some previous studies the Mesenchymal stem cells and neural stem cells. In this study, we have designed an experiment to assess the combination cell therapy (Mesenchymal and Neural stem cells) effects on brain stroke. The Mesenchymal stem cells were isolated from adult rat bone marrow and the neural stem cells were isolated from ganglion eminence of rat embryo 14 days. The Mesenchymal stem cells were injected 1 day after middle cerebral artery occlusion (MCAO) and the neural stem cells transplanted 7 day after MCAO. After 28 days, the neurological outcomes and brain lesion volumes were evaluated. Also, the activity of Caspase 3 was assessed in different groups. The group which received combination cell therapy had better neurological examination and less brain lesion. Also the combination cell therapy group had the least Caspase 3 activity among the groups. The combination cell therapy is more effective than Mesenchymal stem cell therapy and neural stem cell therapy separately in treating the brain stroke in rats.

Binding and internalization of nerve growth factor by PC12 cells

International Nuclear Information System (INIS)

Kasaian, M.T.

1987-01-01

The interaction of nerve growth factor (NGF) with its cell surface receptors has been studied using both fluorescent- and radio-labelled NGF. The fluorescence studies were done by flow cytometry, and gave information about the concentration dependence and time course of NGF binding to rat pheochromocytoma cells (PC12) and human melanoma cells (A875). 125 I-NGF was used to study the fate of NGF in PC12 cells following its association with cell surface receptors. Variations of the PC12 binding assay were used to distinguish ligand bound to fast and slowly dissociating receptors at the cell surface, internalized ligand, and cytoskeletally-associated NGF. Ligand uptake into each of these pools was followed in untreated cells, as well as in cells exposed to colchicine and/or cytochalasin B to disrupt the cytoskeleton. NGF degradation was also followed in these cells, and chloroquine was used to inhibit this process. In a separate project, NGF activity was assayed in samples of human amniotic fluid and cerebrospinal fluid (CSF). A range of activities was found in these samples, with the CSF samples containing somewhat more activity than the amniotic fluid samples

Coexistence of pheochromocytoma/praganglioma and renal artery stenosis

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Vijaya Sarathi

2012-01-01

Full Text Available Renal artery stenosis (RAS often coexists with pheochromocytoma (Pheo/paraganglioma (PGL and often alters the management of patients with Pheo/PGL. We have studied the prevalence of RAS in our Pheo/PGL patients. The study included 70 consecutive, histopathologically proven Pheo/PGL patients from a tertiary health care center. In 60 patients, tumors were limited to adrenal glands (54 unilateral and 6 bilateral while other 10 patients had extra-adrenal abdominal tumors. Five patients had RAS with an overall prevalence of 14%. Only two out of 60 patients with Pheo had RAS with a low prevalence of 3.3% while three out of 10 patients with extra-adrenal abdominal PGL had RAS with a prevalence of 30%. To conclude, RAS commonly coexists with Pheo/PGL, more often with extra-adrenal PGL.

Nine pheochromocytomas in the same patient. Final mapping with ultrasound and angiography

DEFF Research Database (Denmark)

Nolsøe, C P; Jensen, L T; Torp-Pedersen, S

1988-01-01

A 37-year-old man presented with hypertension and elevated urine catecholamine. Ultrasound scanning revealed a solid tumour of the right adrenal gland and two solid tumours in the retroperitoneum. The findings were confirmed with computed tomography and abdominal angiography. At surgery only...... the tumour of the right adrenal gland was removed. The histopathologic diagnosis was pheochromocytoma. Postoperatively the symptoms and biochemistry were unchanged and the patient was referred for further treatment. At ultrasonography and abdominal aortography 6 remaining tumours were demonstrated. Surgery...

Interactions of ozone and antineoplastic drugs on rat lung fibroblasts and Walker rat carcinoma cells

International Nuclear Information System (INIS)

Wenzel, D.G.; Morgan, D.L.

1983-01-01

Cultured rat lung fibroblasts (F-cells) and Walker rat carcinoma cells (WRC-cells) labeled with 51 Cr were exposed to the following antitumor drugs alone or with O 3 : carmustine (BCNU), doxorubicin (Dox), cisplatin (CPt), mitomycin C (Mit C) or vitamin K 3 (Vit K). Release of 51 Cr (cell injury) was greater for F-cells than WRC-cells with any single treatment. Pretreatment with any drug (400 microM), except for Vit K with WRC-cells, did not significantly increase O 3 -induced loss of 51 Cr. Co-exposure of F-cells to drugs and O 3 resulted in a marked potentiation of O 3 -induced injury with Vit K, and an inhibition with Dox

MANAGEMENT OF ENDOCRINE DISEASE: Recurrence or new tumors after complete resection of pheochromocytomas and paragangliomas: a systematic review and meta-analysis.

Science.gov (United States)

Amar, Laurence; Lussey-Lepoutre, Charlotte; Lenders, Jacques W M; Djadi-Prat, Juliette; Plouin, Pierre-Francois; Steichen, Olivier

2016-10-01

To systematically review the incidence and factors associated with recurrences or new tumors after apparent complete resection of pheochromocytoma or thoraco-abdomino-pelvic paraganglioma. A systematic review and meta-analysis of published literature was performed. Pubmed and Embase from 1980 to 2012 were searched for studies published in English on patients with non-metastatic pheochromocytoma or thoraco-abdomino-pelvic paraganglioma, complete tumor resection, postoperative follow-up exceeding 1 month, and recurrence or new tumor documented by pathology, hormonal dosages, or imaging tests. Incidence rates of new events after curative surgery were calculated for each study that had sufficient information and pooled using random-effect meta-analysis. In total, 38 studies were selected from 3518 references, of which 36 reported retrospective cohorts from the USA, Europe, and Asia. Patient follow-up was neither standardized nor exhaustive in the included studies. A clear description of patient retrieval methods was available for nine studies and the follow-up protocol and patient flow for four studies. Only two studies used multivariable methods to assess potential predictors of postoperative events.The overall rate of recurrent disease from 34 studies was 0.98 events/100 person-years (95% confidence interval 0.71, 1.25). Syndromic diseases and paragangliomas were consistently associated with a higher risk of a new event in individual studies and in meta-regression analysis. The risk of recurrent disease after complete resection of pheochromocytoma may be lower than that previously estimated, corresponding to five events for 100 patients followed up for 5 years after complete resection. Risk stratification is required to tailor the follow-up protocol after complete resection of a pheochromocytoma or paraganglioma. Large multicenter studies are needed to this end. © 2016 European Society of Endocrinology.

Immunity to Schistosoma mansoni in congenitally athymic, irradiated and mast cell-depleted rats

International Nuclear Information System (INIS)

Ford, M.J.; Bickle, Q.D.; Taylor, M.G.

1987-01-01

Immunity to Schistosoma mansoni was investigated in congenitally athymic (Nu/Nu) rats, irradiated rats and in mast cell-depleted rats. Nu/Nu rats failed to develop significant resistance following vaccination with irradiated cercariae, although Nu/Nu recipients of serum from vaccinated Fischer rats (VRS) manifested resistance comparable to heterozygous controls, suggesting that T-cells were required in the induction of resistance but were not involved in the efferent arm of antibody-dependent elimination. Radiosensitive cells (including eosinophils, basophils, neutrophils, lymphocytes and mast cells) were apparently not essential for the antibody-dependent elimination of lung or post-lung stages since irradiated (700-750 rad.) recipients of VRS manifested comparable degrees of resistance to unirradiated controls in spite of a greater than 85% reduction in total blood leucocyte counts after irradiation. Depletion of 99% of tissue mast cells by treatment of rats with Compound 48/80 had no significant effect on the attrition of a challenge infection in rats rendered immune by vaccination with irradiated cercariae or by transfer of VRS. However, there was a significant increase in worm recovery in unimmunized and mast cell-depleted or irradiated rats, indicating that mast cells and perhaps other radio-isotope sensitive cells may be involved in innate resistance. (author)

Immunity to Schistosoma mansoni in congenitally athymic, irradiated and mast cell-depleted rats

Energy Technology Data Exchange (ETDEWEB)

Ford, M.J.; Bickle, Q.D.; Taylor, M.G.

1987-04-01

Immunity to Schistosoma mansoni was investigated in congenitally athymic (Nu/Nu) rats, irradiated rats and in mast cell-depleted rats. Nu/Nu rats failed to develop significant resistance following vaccination with irradiated cercariae, although Nu/Nu recipients of serum from vaccinated Fischer rats (VRS) manifested resistance comparable to heterozygous controls, suggesting that T-cells were required in the induction of resistance but were not involved in the efferent arm of antibody-dependent elimination. Radiosensitive cells (including eosinophils, basophils, neutrophils, lymphocytes and mast cells) were apparently not essential for the antibody-dependent elimination of lung or post-lung stages since irradiated (700-750 rad.) recipients of VRS manifested comparable degrees of resistance to unirradiated controls in spite of a greater than 85% reduction in total blood leucocyte counts after irradiation. Depletion of 99% of tissue mast cells by treatment of rats with Compound 48/80 had no significant effect on the attrition of a challenge infection in rats rendered immune by vaccination with irradiated cercariae or by transfer of VRS. However, there was a significant increase in worm recovery in unimmunized and mast cell-depleted or irradiated rats, indicating that mast cells and perhaps other radio-isotope sensitive cells may be involved in innate resistance.

The effects of functional magnetic nanotubes with incorporated nerve growth factor in neuronal differentiation of PC12 cells

International Nuclear Information System (INIS)

Xie Jining; Chen Linfeng; Varadan, Vijay K; Yancey, Justin; Srivatsan, Malathi

2008-01-01

In this in vitro study the efficiency of magnetic nanotubes to bind with nerve growth factor (NGF) and the ability of NGF-incorporated magnetic nanotubes to release the bound NGF are investigated using rat pheochromocytoma cells (PC12 cells). It is found that functional magnetic nanotubes with NGF incorporation enabled the differentiation of PC12 cells into neurons exhibiting growth cones and neurite outgrowth. Microscope observations show that filopodia extending from neuron growth cones were in close proximity to the NGF-incorporated magnetic nanotubes, at times appearing to extend towards or into them. These results show that magnetic nanotubes can be used as a delivery vehicle for NGF and thus may be exploited in attempts to treat neurodegenerative disorders such as Parkinson's disease with neurotrophins. Further neurite outgrowth can be controlled by manipulating magnetic nanotubes with external magnetic fields, thus helping in directed regeneration

Cytosolic Cl- Affects the Anticancer Activity of Paclitaxel in the Gastric Cancer Cell Line, MKN28 Cell

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Sachie Tanaka

2017-05-01

Full Text Available Background/Aims: Our previous study revealed that cytosolic Cl- affected neurite elongation promoted via assembly of microtubule in rat pheochromocytoma PC12D cells and Cl-–induced blockade of intrinsic GTPase enhanced tubulin polymerization in vitro. Paclitaxel (PTX is a microtubule-targeted chemotherapeutic drug and stabilizes microtubules resulting in mainly blockade of mitosis at the metaphase-anaphase transition and induction of apoptosis. In the present study, we tried to clarify whether the cytosolic Cl- affected PTX ability to inhibit cell growth in the gastric cancer cell line, MKN28. Methods: To clarify the cytosolic Cl- action on PTX-induced cell death and metaphase-anaphase transition in the gastric cancer cell line, MKN28 cell, and PTX-induced tubulin polymerization, we performed cell proliferation assay, cytosolic Cl- concentration measurement, immunofluorescence microscopy, and in vitro tubulin polymerization assay. Results: The decline of cytosolic Cl- weakened the cytotoxic effect of PTX on cell proliferation of MKN28 cells, which could pass through the metaphase-anaphase transition. Moreover, in vitro PTX-induced tubulin polymerization was diminished under the low Cl- condition. Conclusions: Our results strongly suggest that the upregulation of cytosolic Cl- concentration would enhance the antitumor effect of PTX, and that the cytosolic Cl- would be one of the key targets for anti-cancer therapy.

Electrofusion of mesenchymal stem cells and islet cells for diabetes therapy: a rat model.

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Goichi Yanai

Full Text Available Islet transplantation is a minimally invasive treatment for severe diabetes. However, it often requires multiple donors to accomplish insulin-independence and the long-term results are not yet satisfying. Therefore, novel ways to overcome these problems have been explored. Isolated islets are fragile and susceptible to pro-apoptotic factors and poorly proliferative. In contrast, mesenchymal stem cells (MSCs are highly proliferative, anti-apoptotic and pluripotent to differentiate toward various cell types, promote angiogenesis and modulate inflammation, thereby studied as an enhancer of islet function and engraftment. Electrofusion is an efficient method of cell fusion and nuclear reprogramming occurs in hybrid cells between different cell types. Therefore, we hypothesized that electrofusion between MSC and islet cells may yield robust islet cells for diabetes therapy. We establish a method of electrofusion between dispersed islet cells and MSCs in rats. The fusion cells maintained glucose-responsive insulin release for 20 days in vitro. Renal subcapsular transplantation of fusion cells prepared from suboptimal islet mass (1,000 islets that did not correct hyperglycemia even if co-transplanted with MSCs, caused slow but consistent lowering of blood glucose with significant weight gain within the observation period in streptozotocin-induced diabetic rats. In the fusion cells between rat islet cells and mouse MSCs, RT-PCR showed new expression of both rat MSC-related genes and mouse β-cell-related genes, indicating bidirectional reprogramming of both β-cell and MSCs nuclei. Moreover, decreased caspase3 expression and new expression of Ki-67 in the islet cell nuclei suggested alleviated apoptosis and gain of proliferative capability, respectively. These results show that electrofusion between MSCs and islet cells yield special cells with β-cell function and robustness of MSCs and seems feasible for novel therapeutic strategy for diabetes

Impact of F DOPA-PET on therapeutic decision in endocrine tumours: digestive tumours, medullary thyroid cancer or pheochromocytoma

International Nuclear Information System (INIS)

Montravers, F.; Grahek, D.; Kerrou, K.; Gutman, F.; Beco, V. de; Nataf, V.; Balard, M.; Talbot, J.N.

2006-01-01

FDOPA-PET has been proposed for a decade in oncology, in particular in endocrine tumours. To the best of our knowledge, only one impact rate has been reported: 31% in 17 patients with digestive carcinoid tumours. We did a questionnaire survey to evaluate this impact reported by the referring clinician in 87 patients who had FDOPA PET due to digestive carcinoid tumour or another type of digestive endocrine tumour or a medullary thyroid cancer or a pheochromocytoma. The response rate to the survey was 87%. The overall impact of FDOPA PET on patient's management was 36%. Its value was greater for digestive carcinoid tumour and for medullary thyroid cancer; the number of patients with pheochromocytoma is still limited. In the other digestive endocrine tumours, a change in patient management was less frequent and FDOPA PET should be performed when the other examinations are inconclusive. (author)

Purification of alpha-toxin from Staphylococcus aureus and application to cell permeabilization

International Nuclear Information System (INIS)

Lind, I.; Ahnert-Hilger, G.; Fuchs, G.; Gratzl, M.

1987-01-01

Crude alpha-toxin was produced by Staphylococcus aureus, strain Wood 46. The amount of exotoxin was monitored during growth and all subsequent purification steps by determination of its hemolytic activity against rabbit erythrocytes. The culture supernatant was treated with ammonium sulfate (75% saturation). The resulting precipitate was dialyzed and subjected to cation-exchange chromatography. The fractions containing the hemolytic activity were further purified by gel chromatography. The final product was enriched by a factor of 8.5 compared to the crude toxin. In sodium dodecyl sulfate-polyacrylamide gel electrophoresis the purified toxin exhibited one major band. It caused the release of 86 Rb+ and ATP from rat insulinoma (RIN A2) as well as pheochromocytoma cells (PC12) in culture, indicating efficient permeabilization of their plasma membranes for small molecules

Characterization and metabolic synthetic lethal testing in a new model of SDH-loss familial pheochromocytoma and paraganglioma.

Science.gov (United States)

Smestad, John; Hamidi, Oksana; Wang, Lin; Holte, Molly Nelson; Khazal, Fatimah Al; Erber, Luke; Chen, Yue; Maher, L James

2018-01-19

Succinate dehydrogenase (SDH)-loss pheochromocytoma and paraganglioma (PPGL) are tumors driven by metabolic derangement. SDH loss leads to accumulation of intracellular succinate, which competitively inhibits dioxygenase enzymes, causing activation of pseudohypoxic signaling and hypermethylation of histones and DNA. The mechanisms by which these alterations lead to tumorigenesis are unclear, however. In an effort to fundamentally understand how SDH loss reprograms cell biology, we developed an immortalized mouse embryonic fibroblast cell line with conditional disruption of Sdhc and characterize the kinetics of Sdhc gene rearrangement, SDHC protein loss, succinate accumulation, and the resultant hypoproliferative phenotype. We further perform global transcriptomic, epigenomic, and proteomic characterization of changes resulting from SDHC loss, identifying specific perturbations at each biological level. We compare the observed patterns of epigenomic derangement to another previously-described immortalized mouse chromaffin cell model of SDHB loss, and compare both models to human SDH-loss tumors. Finally, we perform analysis of SDHC synthetic lethality with lactate dehydrogenase A (LDHA) and pyruvate carboxylase (PCX), which are important for regeneration of NAD+ and aspartate biosynthesis, respectively. Our data show that SDH-loss cells are selectively vulnerable to LDH genetic knock-down or chemical inhibition, suggesting that LDH inhibition may be an effective therapeutic strategy for SDH-loss PPGL.

Derivation of corneal endothelial cell-like cells from rat neural crest cells in vitro.

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Chengqun Ju

Full Text Available The aim of this study was to investigate the feasibility of inducing rat neural crest cells (NCC to differentiate to functional corneal endothelial cell (CEC-like cells in vitro. Rat NCC were induced with adult CEC-derived conditioned medium. Immunofluorescence, flow cytometry and real time RT-PCR assay were used to detect expression of the corneal endothelium differentiation marker N-cadherin and transcription factors FoxC1 and Pitx2. CFDA SE-labeled CEC-like cells were transplanted to the corneal endothelium of a rat corneal endothelium deficiency model, and an eye-down position was maintained for 24 hours to allow cell attachment. The animals were observed for as long as 2 months after surgery and underwent clinical and histological examination. Spindle-like NCC turned to polygonal CEC-like after induction and expressed N-cadherin, FoxC1, Pitx2, zonula occludens-1 and sodium-potassium pump Na(+/K(+ ATPase. The corneas of the experimental group were much clearer than those of the control group and the mean corneal thickness in the experimental group was significantly less than in the control group7, 14, 21 and 28 days after surgery. Confocal microscopy through focusing and histological analysis confirmed that green fluorescence-positive CEC-like cells formed a monolayer covering the Descemet's membrane in the experimental group. In conclusion, CEC-like cells derived from NCCs displayed characters of native CEC, and the induction protocol provides guidance for future human CEC induction from NCC.

Antenatal taurine reduces cerebral cell apoptosis in fetal rats with intrauterine growth restriction.

Science.gov (United States)

Liu, Jing; Wang, Xiaofeng; Liu, Ying; Yang, Na; Xu, Jing; Ren, Xiaotun

2013-08-15

From pregnancy to parturition, Sprague-Dawley rats were daily administered a low protein diet to establish a model of intrauterine growth restriction. From the 12(th) day of pregnancy, 300 mg/kg rine was daily added to food until spontaneous delivery occurred. Brain tissues from normal neonatal rats at 6 hours after delivery, neonatal rats with intrauterine growth restriction, and neonatal rats with intrauterine growth restriction undergoing taurine supplement were obtained for further experiments. The terminal deoxyribonucleotidyl transferase (TdT)-mediated biotin-16-dUTP nick-end labeling assay revealed that the number of apoptotic cells in the brain tissue of neonatal rats with intrauterine growth restriction significantly increased. Taurine supplement in pregnant rats reduced cell apoptosis in brain tissue from neonatal rats with intrauterine growth restriction. nohistochemical staining revealed that taurine supplement increased glial cell line-derived neurotrophic factor expression and decreased caspase-3 expression in the cerebral cortex of intrauterine growth-restricted fetal rats. These results indicate that taurine supplement reduces cell apoptosis through the glial cell line-derived neurotrophic factor-caspase-3 signaling pathway, resulting in a protective effect on the intrauterine growth-restricted fetal rat brain.

Protective effects of red wine flavonols on 4-hydroxynonenal-induced apoptosis in PC12 cells.

Science.gov (United States)

Jang, Young Jin; Kang, Nam Joo; Lee, Ki Won; Lee, Hyong Joo

2009-08-01

There is accumulating evidence that a moderate consumption of red wine has health benefits, such as the inhibition of neurodegenerative diseases. Although this is generally attributed to resveratrol, the protective mechanisms and the active substance(s) remain unclear. We examined whether and how red wine extract (RWE) and red wine flavonols quercetin and myricetin inhibited 4-hydroxynonenal (HNE)-induced apoptosis of rat pheochromocytoma PC12 cells. RWE attenuated HNE-induced PC12 cell death in a dose-dependent manner. HNE induced cleavage of poly(ADP-ribose) polymerase, which is involved in DNA repair in the nucleus, and this was inhibited by RWE treatment. Treatment with RWE also inhibited HNE-induced nuclear condensation in PC12 cells. Data of 2',7'-dichlorofluorescin diacetate showed that RWE protected against apoptosis of PC12 cells by attenuating intracellular reactive oxygen species. The cytoprotective effects on HNE-induced cell death were stronger for quercetin and myricetin than for resveratrol. HNE-induced nuclear condensation was attenuated by quercetin and myricetin. These results suggest that the neuroprotective potential of red wine is attributable to flavonols rather than to resveratrol.

Management of full term pregnant patient with paroxysmal hypertension due to incidental pheochromocytoma

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S. Sahu*

2013-12-01

Case Description: A 25-year-old, full-term pregnant woman diagnosed with pre-eclampsia was referred to our tertiary care hospital with severe resistant hypertension. Her blood pressure remained labile despite the usual medications, which led to the suspicion of an underlying endocrinological problem. Further biochemical and radiological investigations confirmed the diagnosis of pheochromocytoma. The patient was invasively monitored and treated with alpha blockade, beta blocker, and vasodilators in ICU. On the fifth day, she went into spontaneous labour with confirmed rupture of the membranes. The labour was augmented with intravenous oxytocin 2U in 500 ml solution of Ringer’s lactate. A nitro-glycerine basal infusion was started and titrated to control BP during labour to keep the blood pressure below 160/90 mmHg. An injection of Phentolamine drip and beta blocker esmolol was kept ready, to control the wide fluctuation of blood pressure. She delivered a live, healthy, male infant weighing 2.5 Kg. She was kept in the ICU for 72 h with epidural patient-controlled analgesia (EPCA. The patient was not keen for a resection of the adrenal tumour immediately after delivery. She was discharged with medical management, with a further plan for surgery in due course. With a multidisciplinary team approach (gynaecologist, anaesthesiologist, endocrinologist, and surgeon, proper planning, and adequate preoperative medical management; pheochromocytoma in pregnancy can be managed successfully.

Radioprotective effect of calorie restriction in Hela cells and SD rats

International Nuclear Information System (INIS)

Yang Yang; Chong Yu; Jiao Yang; Xu Jiaying; Fan Saijun

2012-01-01

Objective: To explore the effect of low calorie metabolism on the survival of HeLa cells exposed to X-rays, and the influence of starvation on the antioxidative factors in the blood of rats after irradiation. Methods: MTT method was used to evaluate the impact of different concentration glucose on the proliferation of HeLa cells. Colony formation assay was employed to detect the influence of glucose (1, 5, 10 and 25 mmol/L) on radiosensitivity of HeLa cells. Flow cytometry assay was used to analyze distribution of cell cycle and apoptosis. 60 male SD rats were randomly divided into 6 groups with 10 rats each. Rats in every two groups were fed ad libitum, fasted for 24 h and fasted for 48 h, respectively. Rats in one group of each approach were respectively exposed to whole-body X-rays at 11 Gy. At 2 h after irradiation,all of rats were sacrificed and their venous blood was collected. Elisa kits were used to detect superoxide dismutase (SOD) and total antioxidant capacity (T-AOC). Results: An increased viability was observed in HeLa cells treated with the glucose at low concentration (<25 mmol/L), while HeLa cell growth was inhibited by glucose at doses of >25 mmol/L. Relevant to cells treated with 1 mmoL/L glucose, SERs (sensitive enhancement ratio) in cells exposed to 5, 10 and 25 mmol/L glucose were 1.07, 1.10 and 1.23,respectively. A reduction of G 2 /M and S arrests and apoptosis caused by 6 Gy X-ray irradiation were observed [(49.68 ±1.88)% and (35.54±1.45)% at G 2 /M phase, (16.88 ±1.22)% and (10.23 ±1.65)% at S phase, t=10.42, 5.61, P<0.05] and in the cells treated with 1 mmol/L glucose compared with cells treated with 25 mmol/L glucose [(25.50 ± 0.95)% and (7.56 ± 1.07)%, t=21.72, P<0.05].Without irradiation, calorie restriction exhibited a negligible influence on SOD and T-AOC in rats. However, after 11 Gy irradiation, compared with rats fed ad libitum, the levels of SOD and T-AOC were significantly increased in rats with calorie restriction (t=40

Inhibition of Cdc42 and Rac1 activities in pheochromocytoma, the adrenal medulla tumor.

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Croisé, Pauline; Brunaud, Laurent; Tóth, Petra; Gasman, Stéphane; Ory, Stéphane

2017-04-03

Altered Rho GTPase signaling has been linked to many types of cancer. As many small G proteins, Rho GTPases cycle between an active and inactive state thanks to specific regulators that catalyze exchange of GDP into GTP (Rho-GEF) or hydrolysis of GTP into GDP (Rho-GAP). Recent studies have shown that alteration takes place either at the level of Rho proteins themselves (expression levels, point mutations) or at the level of their regulators, mostly RhoGEFs and RhoGAPs. Most reports describe Rho GTPases gain of function that may participate to the tumorigenesis processes. In contrast, we have recently reported that decreased activities of Cdc42 and Rac1 as well as decreased expression of 2 Rho-GEFs, FARP1 and ARHGEF1, correlate with pheochromocytomas, a tumor developing in the medulla of the adrenal gland (Croisé et al., Endocrine Related Cancer, 2016). Here we highlight the major evidence and further study the correlation between Rho GTPases activities and expression levels of ARHGEF1 and FARP1. Finally we also discuss how the decrease of Cdc42 and Rac1 activities may help human pheochromocytomas to develop and comment the possible relationship between FARP1, ARHGEF1 and the 2 Rho GTPases Cdc42 and Rac1 in tumorigenesis.

Transdifferentiated rat pancreatic progenitor cells (AR42J-B13/H) respond to phenobarbital in a rat hepatocyte-specific manner.

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Osborne, M; Haltalli, M; Currie, R; Wright, J; Gooderham, N J

2016-07-01

Phenobarbital (PB) is known to produce species-specific effects in the rat and mouse, being carcinogenic in certain mouse strains, but only in rats if treated after a DNA damaging event. PB treatment in the rat and mouse also produces disparate effects on cell signalling and miRNA expression profiles. These responses are induced by short term and prolonged PB exposure, respectively, with the latter treatments being difficult to examine mechanistically in primary hepatocytes due to rapid loss of the original hepatic phenotype and limited sustainability in culture. Here we explore the rat hepatocyte-like B13/H cell line as a model for hepatic response to PB exposure in both short-term and longer duration treatments. We demonstrate that PB with Egf treatment in the B13/H cells resulted in a significant increase in Erk activation, as determined by the ratio of phospho-Erk to total Erk, compared to Egf alone. We also show that an extended treatment with PB in the B13/H cells produces a miRNA response similar to that seen in the rat in vivo, via the time-dependent induction of miR-182/96. Additionally, we confirm that B13/H cells respond to Car activators in a typical rat-specific manner. These data suggest that the B13/H cells produce temporal responses to PB that are comparable to those reported in short-term primary rat hepatocyte cultures and in the longer term are similar to those in the rat in vivo. Finally, we also show that Car-associated miR-122 expression is decreased by PB treatment in B13/H cells, a PB-induced response that is common to the rat, mouse and human. We conclude that the B13/H cell system produces a qualitative response comparable to the rat, which is different to the response in the mouse, and that this model could be a useful tool for exploring the functional consequences of PB-sensitive miRNA changes and resistance to PB-mediated tumours in the rat. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Effects of voluntary wheel running on satellite cells in the rat plantaris muscle.

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Kurosaka, Mitsutoshi; Naito, Hisashi; Ogura, Yuji; Kojima, Atsushi; Goto, Katsumasa; Katamoto, Shizuo

2009-01-01

This study investigated the effects of voluntary wheel running on satellite cells in the rat plantaris muscle. Seventeen 5-week-old male Wistar rats were assigned to a control (n = 5) or training (n = 12) group. Each rat in the training group ran voluntarily in a running-wheel cage for 8 weeks. After the training period, the animals were anesthetized, and the plantaris muscles were removed, weighed, and analyzed immunohistochemically and biochemically. Although there were no significant differences in muscle weight or fiber area between the groups, the numbers of satellite cells and myonuclei per muscle fiber, percentage of satellite cells, and citrate synthase activity were significantly higher in the training group compared with the control group (p run in the training group (r = 0.61, p running can induce an increase in the number of satellite cells without changing the mean fiber area in the rat plantaris muscle; this increase in satellite cell content is a function of distance run. Key pointsThere is no study about the effect of voluntary running on satellite cells in the rat plantaris muscle.Voluntary running training causes an increase of citrate synthase activity in the rat plantaris muscle but does not affect muscle weight and mean fiber area in the rat plantaris muscle.Voluntary running can induce an increase in the number of satellite cells without hypertrophy of the rat plantaris muscle.

Rat visceral yolk sac cells: viability and expression of cell markers during maternal diabetes

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Aires, M.B. [Departamento de Morfologia, Universidade Federal de Sergipe, São Cristóvão, SE (Brazil); Santos, J.R.A. [Departamento de Enfermagem, Universidade Federal de Sergipe, São Cristóvão, SE (Brazil); Souza, K.S.; Farias, P.S. [Departamento de Morfologia, Universidade Federal de Sergipe, São Cristóvão, SE (Brazil); Santos, A.C.V. [Departamento de Enfermagem, Universidade Federal de Sergipe, São Cristóvão, SE (Brazil); Fioretto, E.T. [Departamento de Morfologia, Universidade Federal de Sergipe, São Cristóvão, SE (Brazil); Maria, D.A. [Laboratório de Bioquímica e Biofísica, Instituto Butantan, São Paulo, SP (Brazil)

2015-07-10

The function of the visceral yolk sac (VYS) is critical for embryo organogenesis until final fetal development in rats, and can be affected by conditions such as diabetes. In view of the importance of diabetes during pregnancy for maternal and neonatal health, the objective of this study was to assess fetal weight, VYS cell markers, and viability in female Wistar rats (200-250 g) with induced diabetes (alloxan, 37 mg/kg) on the 8th gestational day (gd 8). At gd 15, rats from control (n=5) and diabetic (n=5) groups were anesthetized and laparotomized to remove the uterine horns for weighing of fetuses and collecting the VYS. Flow cytometry was used for characterizing VYS cells, and for determining mitochondrial activity, cell proliferation, DNA ploidy, cell cycle phases, and caspase-3 activity. Fetal weight was reduced in the diabetic group. Expression of the cell markers CD34, VEGFR1, CD115, CD117, CD14, CCR2, CD90, CD44, STRO-1, OCT3/4, and Nanog was detected in VYS cells in both groups. In the diabetic group, significantly decreased expression of CD34 (P<0.05), CCR2 (P<0.001), and OCT3/4 (P<0.01), and significantly increased expression of CD90 (P<0.05), CD117 (P<0.01), and CD14 (P<0.05) were observed. VYS cells with inactive mitochondria, activated caspase-3, and low proliferation were present in the rats with diabetes. Severe hyperglycemia caused by maternal diabetes had negative effects on pregnancy, VYS cell viability, and the expression of cell markers.

Rat visceral yolk sac cells: viability and expression of cell markers during maternal diabetes

International Nuclear Information System (INIS)

Aires, M.B.; Santos, J.R.A.; Souza, K.S.; Farias, P.S.; Santos, A.C.V.; Fioretto, E.T.; Maria, D.A.

2015-01-01

The function of the visceral yolk sac (VYS) is critical for embryo organogenesis until final fetal development in rats, and can be affected by conditions such as diabetes. In view of the importance of diabetes during pregnancy for maternal and neonatal health, the objective of this study was to assess fetal weight, VYS cell markers, and viability in female Wistar rats (200-250 g) with induced diabetes (alloxan, 37 mg/kg) on the 8th gestational day (gd 8). At gd 15, rats from control (n=5) and diabetic (n=5) groups were anesthetized and laparotomized to remove the uterine horns for weighing of fetuses and collecting the VYS. Flow cytometry was used for characterizing VYS cells, and for determining mitochondrial activity, cell proliferation, DNA ploidy, cell cycle phases, and caspase-3 activity. Fetal weight was reduced in the diabetic group. Expression of the cell markers CD34, VEGFR1, CD115, CD117, CD14, CCR2, CD90, CD44, STRO-1, OCT3/4, and Nanog was detected in VYS cells in both groups. In the diabetic group, significantly decreased expression of CD34 (P<0.05), CCR2 (P<0.001), and OCT3/4 (P<0.01), and significantly increased expression of CD90 (P<0.05), CD117 (P<0.01), and CD14 (P<0.05) were observed. VYS cells with inactive mitochondria, activated caspase-3, and low proliferation were present in the rats with diabetes. Severe hyperglycemia caused by maternal diabetes had negative effects on pregnancy, VYS cell viability, and the expression of cell markers

Malign pheochromocytoma: importance of the scintigraphic follow-up with metaiodobenzulguanidine 131I (MIBG-131I)

International Nuclear Information System (INIS)

Kato, M.; Velhote, V.V.; Souto, F.J.P.; Long, Y.J.; Costa, P.L.A.

1989-01-01

The authors report a case of pheochromocytoma investigated with metaiodobenzylguanidine labeled with 131 I (MIBG- 131 I). The methodology identify primitive lesion, its recurrence and metastasis. The authors mention the advantage of the technique due to the high specificity, sensitivity and because it is harmless, offering optimal information about the morphology and functional nature, concerning diagnosis and follow-up of the disease. (author) [pt

Chimeric ZHHH neuroglobin acts as a cell membrane-penetrating inducer of neurite outgrowth.

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Takahashi, Nozomu; Onozuka, Wataru; Watanabe, Seiji; Wakasugi, Keisuke

2017-09-01

Neuroglobin (Ngb) is a heme protein expressed in the vertebrate brain. We previously engineered a chimeric Ngb protein, in which module M1 of human Ngb is replaced by that of zebrafish Ngb, and showed that the chimeric ZHHH Ngb has a cell membrane-penetrating activity similar to that of zebrafish Ngb and also rescues cells from death caused by hypoxia/reoxygenation as does human Ngb. Recently, it was reported that overexpression of mammalian Ngb in neuronal cells induces neurite outgrowth. In this study, we performed neurite outgrowth assays of chimeric Ngb using rat pheochromocytoma PC12 cells. Addition of chimeric Ngb, but not human or zebrafish Ngb, exogenously to the cell medium induces neurite outgrowth. On the other hand, the K7A/K9Q chimeric Ngb double mutant, which cannot translocate into cells, did not induce neurite outgrowth, suggesting that the cell membrane-penetrating activity of the chimeric Ngb is crucial for its neurite outgrowth-promoting activity. We also prepared several site-directed chimeric Ngb mutants and demonstrated that residues crucial for neurite outgrowth-inducing activity of the chimeric Ngb are not exactly the same as those for its neuroprotective activity.

high doses of prolactin inhibit testosterone secretion in rat leydig cells

African Journals Online (AJOL)

Femi Olaleye

1 The effect of prolactin on dispersed rat Leydig cells was investigated. Leydig cells from adult rat testes of proven fertility were isolated via collagenase digestion and dispersion. About 100,000 Leydig .... Hormones, Drugs and Reagents.

Pheochromocytoma treated by laparoscopic surgery Feocromocitoma tratado por cirurgia laparoscópica

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Lísias Nogueira Castilho

2000-06-01

Full Text Available OBJECTIVE: To evaluate the results of the laparoscopic technique in the treatment of adrenal pheochromocytoma. METHOD: Ten patients, 7 men and 3 women, between 10 and 67 years of age (mean 48 with pheochromocytoma underwent transperitoneal laparoscopic adrenalectomy and were evaluated retrospectively, based on clinical, laboratory, and pathological diagnosis. In all cases there was a solid unilateral adrenal tumor, 5 on the left side and 5 on the right side, whose greater diameter varied from 7 to 80 mm (mean 32. Nine of the 10 patients were chronically hypertensive or had already had hypertensive crises. One patient was normotensive, but presented metabolic alterations suggestive of adrenergic hyperfunction. RESULTS: No deaths occurred in this series. There were two (20% conversions to open surgery, one due to venous bleeding and one due to the difficulty of dissection behind the vena cava in a patient presenting a partially retro-caval tumor. Surgical time in the 8 non-converted cases ranged from 70 to 215 minutes (mean 136. One patient (10% received blood transfusion, and another (10% presented two complications - acute renal failure and a subcutaneous infection. Both had been converted to open surgery. None of the non-converted cases was transfused or presented complications. Hospital discharge occurred between the 2nd and 11th post-operative day (mean 3. The pathological exam of the surgical specimens confirmed the diagnoses of pheochromocytoma in all 10 cases, one of them associated with an aldosterone-producing cortical tumor. CONCLUSIONS: Laparoscopic adrenalectomy for selected patients presenting pheochromocytoma is feasible and provides good results.OBJETIVO: Avaliar os resultados da utilização da técnica laparoscópica no tratamento do feocromocitoma de supra-renal. MÉTODO: Dez pacientes, sete homens e três mulheres, entre 10 e 67 anos de idade (média 48, com feocromocitoma, foram operados por via laparoscópica transperitoneal

Antitumor Activity of Rat Mesenchymal Stem Cells during Direct or Indirect Co-Culturing with C6 Glioma Cells.

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Gabashvili, A N; Baklaushev, V P; Grinenko, N F; Mel'nikov, P A; Cherepanov, S A; Levinsky, A B; Chehonin, V P

2016-02-01

The tumor-suppressive effect of rat mesenchymal stem cells against low-differentiated rat C6 glioma cells during their direct and indirect co-culturing and during culturing of C6 glioma cells in the medium conditioned by mesenchymal stem cells was studied in an in vitro experiment. The most pronounced antitumor activity of mesenchymal stem cells was observed during direct co-culturing with C6 glioma cells. The number of live C6 glioma cells during indirect co-culturing and during culturing in conditioned medium was slightly higher than during direct co-culturing, but significantly differed from the control (C6 glioma cells cultured in medium conditioned by C6 glioma cells). The cytotoxic effect of medium conditioned by mesenchymal stem cells was not related to medium depletion by glioma cells during their growth. The medium conditioned by other "non-stem" cells (rat astrocytes and fibroblasts) produced no tumor-suppressive effect. Rat mesenchymal stem cells, similar to rat C6 glioma cells express connexin 43, the main astroglial gap junction protein. During co-culturing, mesenchymal stem cells and glioma C6 cells formed functionally active gap junctions. Gap junction blockade with connexon inhibitor carbenoxolone attenuated the antitumor effect observed during direct co-culturing of C6 glioma cells and mesenchymal stem cells to the level produced by conditioned medium. Cell-cell signaling mediated by gap junctions can be a mechanism of the tumor-suppressive effect of mesenchymal stem cells against C6 glioma cells. This phenomenon can be used for the development of new methods of cell therapy for high-grade malignant gliomas.

Changes in pituitary growth hormone cells prepared from rats flown on Spacelab 3

Science.gov (United States)

Grindeland, R.; Hymer, W. C.; Farrington, M.; Fast, T.; Hayes, C.; Motter, K.; Patil, L.; Vasques, M.

1987-01-01

The effect of exposure to microgravity on pituitary gland was investigated by examining cells isolated from anterior pituitaries of rats flown on the 7-day Spacelab 3 mission and, subsequently, cultured for 6 days. Compared with ground controls, flight cells contained more intracellular growth hormone (GH); however, the flight cells released less GH over the 6-day culture period and after implantation into hypophysectomized rats than did the control cells. Compared with control rats, glands from large rats (400 g) contained more somatotrophs (44 percent compared with 37 percent in control rats); small rats (200 g) showed no difference. No major differences were found in the somatotroph ultrastructure (by TEM) or in the pattern of the immunoactive GH variants. However, high-performance liquid chromatography fractionation of culture media indicated that flight cells released much less of a biologically active high-molecular weight GH variant, suggesting that space flight may lead to secretory dysfunction.

Management of pediatric pheochromocytoma. A review of the literature

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Mauriello C

2016-06-01

Full Text Available Introduction Pheochromocytoma is a tumor originated from the chromaffin tissue of the adrenal medulla or from extra-adrenal paraganglionic tissue. Pheochromocytomasare extremely rare in the pediatric population, accounting for 1% of pediatric hypertension. Material and Methods The Authors conduced a systematic review of the pediatric PCC focusing on the indications and surgical technique. Results Surgery remains the mainstay of treatment of pheochromocytomain children. Prior to surgery all children must be prepared with alpha-blockade with adequate fluid and salt replacement in order to reduce surgical complications. Discussion and Conclusions Minimally invasive adrenalectomy is the gold standard for benign lesions of the adrenal gland. The lateral transperitoneal adrenalectomy is the standard approach. Laparoscopic bilateral partial adrenalectomies should be considered in children with bilateral PCC in order to avoid lifelong glucocorticoid and mineralocorticoid replacement.

Rapid development of Leydig cell tumors in a Wistar rat substrain

NARCIS (Netherlands)

Teerds, K. J.; de rooij, D. G.; de Jong, F. H.; Rommerts, F. F.

1991-01-01

In 78% of the Wistar rats (substrain U) studied, spontaneous Leydig cell tumors developed between the ages of 12 and 30 months. The first signs of tumor development, in the form of nodules of Leydig cells, were already apparent in 1-month-old U-rats. These nodules of Leydig cells were found in all

Construction of rat beta defensin-2 eukaryotic expression vector and expression in the transfected rat corneal epithelial cell

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Jing Dan

2017-03-01

Full Text Available AIM: To construct a recombinant eukaryotic expression vector of rat beta defensin-2(rBD-2, transfect it into the rat corneal epithelial cells with lipofection, determine the expression of target gene in the transfected cells, and discuss the potentiality of recombinant plasmid expressed in corneal epithelial cells, hoping to provide an experimental foundation for further study on the antimicrobial activity of rBD-2 in vitro and in vivo and to assess the probability of defensins as a new application for infectious corneal diseases in the future. METHODS: The synthetic rBD-2 DNA fragment was inserted between the XhoI and BamHI restriction enzyme cutting sites of eukaryotic expression vector pIRES2-ZsGreen1 to construct the recombinant plasmid pIRES2-ZsGreen1-rBD-2, then transformed it into E.coli DH5α, positive clones were screened by kanamycin and identified with restriction endonucleases and sequencing analysis. Transfection into the rat corneal epithelial cells was performed by lipofection. Then the experiment was divided into three groups: rat corneal epithelial cell was transfected with the recombinant plasmid pIRES2- ZsGreen1-rBD-2, rat corneal epithelial cell was transfected with the empty plasmid pIRES2-ZsGreen1 and the non-transfected group. The inverted fluorescence microscope was used to observe the transfection process. At last, the level of rBD-2 mRNA expressed in the transfected cells and the control groups are compared by the real-time fluoresence relative quantitative PCR. RESULTS: The recombinant eukaryotic expression vector of pIRES2-ZsGreen1-rBD-2 was successfully constructed. The level of rBD-2 mRNA in transfected cells was significantly higher than that in control groups through the real-time fluorescence relative quantitative PCR. CONCLUSION: The recombinant eukaryotic expression vector pIRES2-ZsGreen1-rBD-2 could be transfected into rat corneal epithelial cells, and exogenous rBD-2 gene could be transcripted into mRNA in

Nanotechnology versus stem cell engineering: in vitro comparison of neurite inductive potentials.

Science.gov (United States)

Morano, Michela; Wrobel, Sandra; Fregnan, Federica; Ziv-Polat, Ofra; Shahar, Abraham; Ratzka, Andreas; Grothe, Claudia; Geuna, Stefano; Haastert-Talini, Kirsten

2014-01-01

Innovative nerve conduits for peripheral nerve reconstruction are needed in order to specifically support peripheral nerve regeneration (PNR) whenever nerve autotransplantation is not an option. Specific support of PNR could be achieved by neurotrophic factor delivery within the nerve conduits via nanotechnology or stem cell engineering and transplantation. Here, we comparatively investigated the bioactivity of selected neurotrophic factors conjugated to iron oxide nanoparticles (np-NTFs) and of bone marrow-derived stem cells genetically engineered to overexpress those neurotrophic factors (NTF-BMSCs). The neurite outgrowth inductive activity was monitored in culture systems of adult and neonatal rat sensory dorsal root ganglion neurons as well as in the cell line from rat pheochromocytoma (PC-12) cell sympathetic culture model system. We demonstrate that np-NTFs reliably support numeric neurite outgrowth in all utilized culture models. In some aspects, especially with regard to their long-term bioactivity, np-NTFs are even superior to free NTFs. Engineered NTF-BMSCs proved to be less effective in induction of sensory neurite outgrowth but demonstrated an increased bioactivity in the PC-12 cell culture system. In contrast, primary nontransfected BMSCs were as effective as np-NTFs in sensory neurite induction and demonstrated an impairment of neuronal differentiation in the PC-12 cell system. Our results evidence that nanotechnology as used in our setup is superior over stem cell engineering when it comes to in vitro models for PNR. Furthermore, np-NTFs can easily be suspended in regenerative hydrogel matrix and could be delivered that way to nerve conduits for future in vivo studies and medical application.

Mutation analysis of SDHB and SDHC: novel germline mutations in sporadic head and neck paraganglioma and familial paraganglioma and/or pheochromocytoma

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Wong Nora

2006-01-01

Full Text Available Abstract Background Germline mutations of the SDHD, SDHB and SDHC genes, encoding three of the four subunits of succinate dehydrogenase, are a major cause of hereditary paraganglioma and pheochromocytoma, and demonstrate that these genes are classic tumor suppressors. Succinate dehydrogenase is a heterotetrameric protein complex and a component of both the Krebs cycle and the mitochondrial respiratory chain (succinate:ubiquinone oxidoreductase or complex II. Methods Using conformation sensitive gel electrophoresis (CSGE and direct DNA sequencing to analyse genomic DNA from peripheral blood lymphocytes, here we describe the mutation analysis of the SDHB and SDHC genes in 37 patients with sporadic (i.e. no known family history head and neck paraganglioma and five pheochromocytoma and/or paraganglioma families. Results Two sporadic patients were found to have a SDHB splice site mutation in intron 4, c.423+1G>A, which produces a mis-spliced transcript with a 54 nucleotide deletion, resulting in an 18 amino acid in-frame deletion. A third patient was found to carry the c.214C>T (p.Arg72Cys missense mutation in exon 4 of SDHC, which is situated in a highly conserved protein motif that constitutes the quinone-binding site of the succinate: ubiquinone oxidoreductase (SQR complex in E. coli. Together with our previous results, we found 27 germline mutations of SDH genes in 95 cases (28% of sporadic head and neck paraganglioma. In addition all index patients of five families showing hereditary pheochromocytoma-paraganglioma were found to carry germline mutations of SDHB: four of which were novel, c.343C>T (p.Arg115X, c.141G>A (p.Trp47X, c.281G>A (p.Arg94Lys, and c.653G>C (p.Trp218Ser, and one reported previously, c.136C>T, p.Arg46X. Conclusion In conclusion, these data indicate that germline mutations of SDHB and SDHC play a minor role in sporadic head and neck paraganglioma and further underline the importance of germline SDHB mutations in cases of

Design and fabrication of a microplatform for the proximity effect study of localized ELF-EMF on the growth of in vitro HeLa and PC-12 cells

International Nuclear Information System (INIS)

Chen, Y C; Chen, C C; Cheng, Y T; Tu, W; Tseng, F G

2010-01-01

This paper presents a platform technology with experimental results that show the scientists and biologists a way to rapidly investigate and analyze the biological effects of localized extremely low frequency (ELF) electromagnetic field (EMF) on living cells. The proximity effect of the localized ELF-EMF on living cells is revealed using the bio-compatible microplatform on which an on-glass inductive coil array, the source of the localized ELF-EMF in micro scale, is designed, fabricated and operated with a field strength of 1.2 ± 0.1 mT at 60 Hz for cell culturing study. After a 72 h ELF-EMF exposure, HeLa (human cervical cancer) and PC-12 (rat pheochromocytoma) cells exhibit about 18.4% and 12.9% cell proliferation rate reduction, respectively. Furthermore, according to the presented dynamic model, the reduction of the proliferation can be attributed to the interference of signal transduction processes due to the tangential currents induced around the cells

Mast cells in the sheep, hedgehog and rat forebrain

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MICHALOUDI, HELEN C.; PAPADOPOULOS, GEORGIOS C.

1999-01-01

The study was designed to reveal the distribution of various mast cell types in the forebrain of the adult sheep, hedgehog and rat. Based on their histochemical and immunocytochemical characteristics, mast cells were categorised as (1) connective tissue-type mast cells, staining metachromatically purple with the toluidine blue method, or pale red with the Alcian blue/safranin method, (2) mucosal-type or immature mast cells staining blue with the Alcian blue/safranin method and (3) serotonin immunopositive mast cells. All 3 types of brain mast cells in all species studied were located in both white and grey matter, often associated with intraparenchymal blood vessels. Their distribution pattern exhibited interspecies differences, while their number varied considerably not only between species but also between individuals of each species. A distributional left-right asymmetry, with more cells present on the left side, was observed in all species studied but it was most prominent in the sheep brain. In the sheep, mast cells were abundantly distributed in forebrain areas, while in the hedgehog and the rat forebrain, mast cells were less widely distributed and were relatively or substantially fewer in number respectively. A limited number of brain mast cells, in all 3 species, but primarily in the rat, were found to react both immunocytochemically to 5-HT antibody and histochemically with Alcian blue/safranin staining. PMID:10634696

[Pheochromocytoma and paraganglioma in childhood: a report of 2 cases report].

Science.gov (United States)

Mosquera Gorostidi, A; Justo Ranera, A; Zakirian Denis, S E; González Temprano, N; Sagaseta de Ilúrdoz Uranga, M; Molina Garicano, J

2015-01-01

Pheochromocytomas and paragangliomas are rare neuroendocrine tumors in children and most of them are sporadic. However, they represent the most common endocrine tumor in childhood, and hereditary tumor syndromes are most relevant in these age. Advances in genetic, biochemistry and imaging techniques have revised the management of these tumors; thus A biochemical study should be always initiated once the clinical diagnosis is suspected, followed by imaging and molecular studies, particularly in the context of known familial disease. The diagnostic and therapeutic features are reviewed after the presentation of two clinical cases, where the second one is a patient with type 1 Neurofibromatosis. Copyright © 2014. Published by Elsevier Espana.

Differentiated cells derived from fetal neural stem cells improve motor deficits in a rat model of Parkinson’s disease

Institute of Scientific and Technical Information of China (English)

Wei Wang; Hao Song; Aifang Shen; Chao Chen; Yanming Liu; Yabing Dong; Fabin Han

2015-01-01

Objective: Parkinson’s disease(PD), which is one of the most common neuro‐degenerative disorders, is characterized by the loss of dopamine(DA) neurons in the substantia nigra in the midbrain. Experimental and clinical studies have shown that fetal neural stem cells(NSCs) have therapeutic effects in neurological disorders. The aim of this study was to examine whether cells that were differentiated from NSCs had therapeutic effects in a rat model of PD. Methods: NSCs were isolated from 14‐week‐old embryos and induced to differentiate into neurons, DA neurons, and glial cells, and these cells were characterized by their expression of the following markers: βⅢ‐tubulin and microtubule‐associated protein 2(neurons), tyrosine hydroxylase(DA neurons), and glial fibrillary acidic protein(glial cells). After a 6‐hydroxydopamine(6‐OHDA)‐lesioned rat model of PD was generated, the differentiated cells were transplanted into the striata of the 6‐OHDA‐lesioned PD rats. Results: The motor behaviors of the PD rats were assessed by the number of apomorphine‐induced rotation turns. The results showed that the NSCs differentiated in vitro into neurons and DA neurons with high efficiencies. After transplantation into the striata of the PD rats, the differentiated cells significantly improved the motor deficits of the transplanted PD rats compared to those of the control nontransplanted PD rats by decreasing the apomorphine‐induced turn cycles as early as 4 weeks after transplantation. Immunofluorescence analyses showed that the differentiated DA neurons survived more than 16 weeks. Conclusions: Our results showed that cells that were differentiated from NSCs had therapeutic effects in a rat PD model, which suggests that differentiated cells may be an effective treatment for patients with PD.

Diabetes increases susceptibility of primary cultures of rat proximal tubular cells to chemically induced injury

International Nuclear Information System (INIS)

Zhong Qing; Terlecky, Stanley R.; Lash, Lawrence H.

2009-01-01

Diabetic nephropathy is characterized by increased oxidative stress and mitochondrial dysfunction. In the present study, we prepared primary cultures of proximal tubular (PT) cells from diabetic rats 30 days after an ip injection of streptozotocin and compared their susceptibility to oxidants (tert-butyl hydroperoxide, methyl vinyl ketone) and a mitochondrial toxicant (antimycin A) with that of PT cells isolated from age-matched control rats, to test the hypothesis that PT cells from diabetic rats exhibit more cellular and mitochondrial injury than those from control rats when exposed to these toxicants. PT cells from diabetic rats exhibited higher basal levels of reactive oxygen species (ROS) and higher mitochondrial membrane potential, demonstrating that the PT cells maintain the diabetic phenotype in primary culture. Incubation with either the oxidants or mitochondrial toxicant resulted in greater necrotic and apoptotic cell death, greater evidence of morphological damage, greater increases in ROS, and greater decreases in mitochondrial membrane potential in PT cells from diabetic rats than in those from control rats. Pretreatment with either the antioxidant N-acetyl-L-cysteine or a catalase mimetic provided equivalent protection of PT cells from both diabetic and control rats. Despite the greater susceptibility to oxidative and mitochondrial injury, both cytoplasmic and mitochondrial glutathione concentrations were markedly higher in PT cells from diabetic rats, suggesting an upregulation of antioxidant processes in diabetic kidney. These results support the hypothesis that primary cultures of PT cells from diabetic rats are a valid model in which to study renal cellular function in the diabetic state.

Abnormal G1 arrest in the cell lines from LEC strain rats after X-irradiation

International Nuclear Information System (INIS)

Hayashi, M.; Uehara, K.; Kirisawa, R.; Endoh, D.; Arai, S.; Okui, T.

1997-01-01

The effect of X-irradiation of cell lines from LEC and WKAH strain rats on a progression o cell cycle was investigated. When WKAH rat ells were exposed to 5 Gy of X-rays and their cell cycle distribution was determined by a flow cytometer, the proportion of S-phase cells decrease and that of G2/M-phase cells in creased at 8 hr post-irradiation. At 18 and 24 hr post-irradiation, approximately 80% of the cells appeared in the G1 phase. On the contrary, the proportion of S-phase cells increased and that of G1-phase cells decreased in LEC rats during 8-24 hr post-irradiation, compared with that at 0 hr post-irradiation. Thus, radiation-induced delay in the progression from the G1 phase to S phase (G1 arrest) was observed inWKAH rat cells but not in LEC rat cells. In the case of WKAH rat cells, the intensities of the bands of p53 protein increased at 1 and 2 hr after X-irradiation at 5 Gy, compared with those of un-irradiated cells and at 0 hr post-irradiation. In contrast, the intensities of the bands were faint and did not significantly increase in LEC rat ells during 0-6 hr incubation after X-irradiation. Present results suggested that the radioresistant DNA synthesis in LEC rat cells is thought to be due to the abnormal G1 arrest following X-irradiation

Stimulation of DNA synthesis in cultured rat alveolar type II cells

International Nuclear Information System (INIS)

Leslie, C.C.; McCormick-Shannon, K.; Robinson, P.C.; Mason, R.J.

1985-01-01

Restoration of the alveolar epithelium after injury is thought to be dependent on the proliferation of alveolar type II cells. To understand the factors that may be involved in promoting type II cell proliferation in vivo, we determined the effect of potential mitogens and culture substrata on DNA synthesis in rat alveolar type II cells in primary culture. Type II cells cultured in basal medium containing 10% fetal bovine serum (FBS) exhibited essentially no DNA synthesis. Factors that stimulated 3 H-thymidine incorporation included cholera toxin, epidermal growth factor, and rat serum. The greatest degree of stimulation was achieved by plating type II cells on an extracellular matrix prepared from bovine corneal endothelial cells and then by culturing the pneumocytes in medium containing rat serum, cholera toxin, insulin, and epidermal growth factor. Under conditions of stimulation of 3 H-thymidine incorporation there was an increased DNA content per culture dish but no increase in cell number. The ability of various culture conditions to promote DNA synthesis in type II cells was verified by autoradiography. Type II cells were identified by the presence of cytoplasmic inclusions, which were visualized by tannic acid staining before autoradiography. These results demonstrate the importance of soluble factors and culture substratum in stimulating DNA synthesis in rat alveolar type II cells in primary culture

Protective Effect of Quercetin against Oxidative Stress-Induced Cytotoxicity in Rat Pheochromocytoma (PC-12) Cells

OpenAIRE

Dengke Bao; Jingkai Wang; Xiaobin Pang; Hongliang Liu

2017-01-01

Oxidative stress has been implicated in the pathogenesis of many kinds of neurodegenerative disorders, particularly Parkinson’s disease. Quercetin is a bioflavonoid found ubiquitously in fruits and vegetables, and has antioxidative activity. However, the underlying mechanism of the antioxidative effect of quercetin in neurodegenerative diseases has not been well explored. Here, we investigated the antioxidative effect and underlying molecular mechanisms of quercetin on PC-12 cells. We found t...

Pheochromocytoma and Adrenocortical Adenoma in the Same Gland

Directory of Open Access Journals (Sweden)

Wei-Ren Hwang

2007-07-01

Full Text Available A right adrenal tumor was found incidentally during abdominal computed tomography exam in a 51-year-old female patient, who had had diabetes and hypertension for more than 10 years. The computed tomography scan was arranged for possible pancreatic lesion by a neurologist. Norepinephrine level was high in the plasma and urine. Vanillylmandelic acid level was elevated in the urine. Diurnal cortisol rhythm, plasma adrenocorticotropic hormone and urine free cortisol were all normal, but the plasma cortisol concentration could not be suppressed after a standard low-dose dexamethasone suppression test. Therefore, adrenal cortical adenoma with subclinical Cushing's syndrome was highly suspected; however, further imaging studies, including magnetic resonance image and 131I-6β-iodomethylnorcholesterol adrenal scintigraphy failed to discriminate an additional tumor. After right adrenalectomy, a small adrenal cortical adenoma and a large pheochromocytoma were noted. This is an extremely rare case of an adrenal incidentaloma consisting of both medullary and cortical tumors in the same gland.

Formation of binucleated myocardial cells in the neonatal rat. An index for growth hypertrophy

International Nuclear Information System (INIS)

Clubb, F.J. Jr.; Bishop, S.P.

1984-01-01

The purposes of this study were to characterize myocardial cell growth in neonatal rats and investigate the mechanism of binucleation in myocardial cells. To test the hypothesis that binucleated myocardial cells result from karyokinesis without cytokinesis, experiments were designed to measure the rate of DNA synthesis and the percentage of binucleated myocardial cells in neonatal rats during growth. Estimates of myocardial cell nuclear divisions were obtained from rats pulsed with tritiated thymidine at 17 days of gestation. Autoradiograms were prepared from isolated myocardial cells of rats killed at various ages postpartum, and the number of developed silver halide grains over myocardial cell nuclei was calculated. This estimated the mitotic activity of nuclei. To determine myocardial cell DNA synthesis postpartum, another set of rats were injected at various time periods with 4 hourly doses of tritiated thymidine, and hearts were fixed by perfusion 1 hour later. Labeling index of myocardial cells was calculated (labeled/total myocardial cells) from autoradiograms. Results indicated that the growth of myocardial cells in period can be divided into three phases: (a) a hyperplastic phase, (b) a transitional phase, and (c) a hypertrophic phase. Binucleation of myocardial cells was not due to fusion of mononucleated cells

Neurotrophin release by neurotrophins: Implications for activity-dependent neuronal plasticity

OpenAIRE

Canossa, Marco; Griesbeck, Oliver; Berninger, Benedikt; Campana, Gabriele; Kolbeck, Roland; Thoenen, Hans

1997-01-01

Neurotrophins, secreted in an activity-dependent manner, are thought to be involved in the activity-dependent refinement of synaptic connections. Here we demonstrate that in hippocampal neurons and the rat pheochromocytoma cell line PC12 application of exogenous neurotrophins induces secretion of neurotrophins, an effect that is mediated by the activation of tyrosine kinase neurotrophin receptors (Trks). Like activity-dependent secretion of neurotrophins, neurotrophin-induced neurotrophin sec...

A method for isolating identifying and culturing of rat trachea-bronchia epithelial cells

International Nuclear Information System (INIS)

Cui Fengmei; Su Shibiao; Nie Jihua; Li Bingyan; Tong Jian

2005-01-01

Objective: To explore a method for isolating identifying and culturing the rat trachea-bronchia epithelial cells. Methods: The rat trachea-bronchia epithelial cells were isolated by digestion with pronase and brushing with cell brush, identified using confocul and cultured in entire F12 media with no serum. Results: With this method, cells in high purity and high viability could be obtained, and about 10 6 cells per rat. The cells grow well in entire F12 media with no serum. Conclusion: The method is useful for isolating rate trachea-bronchia epithelial cells and the entire F12 media with no serum is effective for culturing. (authors)

Elevated hydrostatic pressures induce apoptosis and oxidative stress through mitochondrial membrane depolarization in PC12 neuronal cells: A cell culture model of glaucoma.

Science.gov (United States)

Tök, Levent; Nazıroğlu, Mustafa; Uğuz, Abdülhadi Cihangir; Tök, Ozlem

2014-10-01

Despite the importance of oxidative stress and apoptosis through mitochondrial depolarization in neurodegenerative diseases, their roles in etiology of glaucoma are poorly understood. We aimed to investigate whether oxidative stress and apoptosis formation are altered in rat pheochromocytoma-derived cell line-12 (PC12) neuronal cell cultures exposed to elevated different hydrostatic pressures as a cell culture model of glaucoma. Cultured PC12 cells were subjected to 0, 15 and 70 mmHg hydrostatic pressure for 1 and 24 h. Then, the following values were analyzed: (a) cell viability; (b) lipid peroxidation and intracellular reactive oxygen species production; (c) mitochondrial membrane depolarization; (d) cell apoptosis; (e) caspase-3 and caspase-9 activities; (f) reduced glutathione (GSH) and glutathione peroxidase (GSH-Px). The hydrostatic pressures (15 and 70 mmHg) increased oxidative cell damage through a decrease of GSH and GSH-Px values, and increasing mitochondrial membrane potential. Additionally, 70 mmHg hydrostatic pressure for 24 h indicated highest apoptotic effects, as demonstrated by plate reader analyses of apoptosis, caspase-3 and -9 values. The present data indicated oxidative stress, apoptosis and mitochondrial changes in PC12 cell line during different hydrostatic pressure as a cell culture model of glaucoma. This findings support the view that mitochondrial oxidative injury contributes early to glaucomatous optic neuropathy.

T cell dysfunction in the diabetes-prone BB rat. A role for thymic migrants that are not T cell precursors

International Nuclear Information System (INIS)

Georgiou, H.M.; Lagarde, A.C.; Bellgrau, D.

1988-01-01

Diabetes-prone BB (BB-DP) rats express several T cell dysfunctions which include poor proliferative and cytotoxic responses to alloantigen. The goal of this study was to determine the origin of these T cell dysfunctions. When BB-DP rats were thymectomized, T cell depleted, and transplanted with neonatal thymus tissue from diabetes-resistant and otherwise normal DA/BB F1 rats, the early restoration of T cell function proceeded normally on a cell-for-cell basis; i.e., peripheral T cells functioned like those from the thymus donor. Because the thymus in these experiments was subjected to gamma irradiation before transplantation and there was no evidence of F1 chimerism in the transplanted BB-DP rats, it appeared that the BB-DP T cell precursors could mature into normally functioning T cells if the maturation process occurred in a normal thymus. If the F1 thymus tissue was treated with dGua before transplantation, the T cells of these animals functioned poorly like those from untreated BB-DP rats. dGua poisons bone marrow-derived cells, including gamma radiation-resistant cells of the macrophage/dendritic cell lineages, while sparing the thymic epithelium. Therefore, the reversal of the T cell dysfunction depends on the presence in the F1 thymus of gamma radiation-resistant, dGua-sensitive F1 cells. Conversely, thymectomized and T cell-depleted F1 rats expressed T cell dysfunction when transplanted with gamma-irradiated BB thymus grafts. T cell responses were normal in animals transplanted with dGua-treated BB thymus grafts. With increasing time after thymus transplantation, T cells from all animals gradually expressed the functional phenotype of the bone marrow donor. Taken together these results suggest that BB-DP bone marrow-derived cells that are not T cell precursors influence the maturation environment in the thymus of otherwise normal BB-DP T cell precursors

[Effects of tributyltin chloride (TBT) and triphenyltin chloride (TPT) on rat testicular Leydig cells].

Science.gov (United States)

Wang, Bao-an; Li, Ming; Mu, Yi-ming; Lu, Zhao-hui; Li, Jiang-yuan

2006-06-01

To investigate the effects of tributyltin chloride (TBT) and triphenyltin chloride (TPT) on rat testicular Leydig cells. The rat Leydig cells (LC-540) were incubated with 0 to 80 nmol/L TBT and TPT for 24 to approximately 96 h, and then the cell viability was determined by MTT. DNA fragmentation ladder formation of cell apoptosis was examined by agarose electrophoresis. Effects of chelator of intracellular Ca2+ (BAPTA) and the inhibitors of PKA, PKC and TPK on cell apoptosis induced by TBT were observed. Effects of TBT on testosterone production in primary cultured rat Leydig cells treated with or without hCG were detected. TBT and TPT suppressed Leydig cell survival in a time- and dose-dependent manner. The suppressive effects of TBT and TPT on the cell survival was caused by apoptosis which was determined by DNA ladder formation. The apoptotic effect of TBT was possibly mediated by the rise in intracellular Ca2+ because it could be blocked by BAPTA, the chelator of intracellular Ca2+; PKA, PKC and TPK inhibitors did not prevent the apoptotic effects induced by TBT. TBT markedly suppressed testosterone production of primary cultured rat Leydig cells with or without hCG stimulation. TBT and TPT induced apoptosis in rat testicular Leydig cells possibly through increasing intracellular Ca2+. TBT reduced the testosterone production of rat Leydig cells.

Moringa oleifera-rich diet and T cell calcium signaling in spontaneously hypertensive rats.

Science.gov (United States)

Attakpa, E S; Bertin, G A; Chabi, N W; Ategbo, J-M; Seri, B; Khan, N A

2017-11-24

Moringa oleifera is a plant whose fruits, roots and leaves have been advocated for traditional medicinal uses. The physicochemical analysis shows that Moringa oleifera contains more dietary polyunsaturated fatty acids (PUFA) than saturated fatty acids (SFA). The consumption of an experimental diet enriched with Moringa oleifera extracts lowered blood pressure in spontaneously hypertensive rats (SHR), but not in normotensive Wistar-Kyoto (WKY) rats as compared to rats fed an unsupplemented control diet. Anti-CD3-stimulated T cell proliferation was diminished in both strains of rats fed the Moringa oleifera. The experimental diet lowered secretion of interleukin-2 in SHR, but not in WKY rats compared with rats fed the control diet. Studies of platelets from patients with primary hypertension and from SHR support the notion that the concentration of intracellular free calcium [Ca(2+)](i) is modified in both clinical and experimental hypertension. We observed that the basal, [Ca(2+)](i) was lower in T cells of SHR than in those of WKY rats fed the control diet. Feeding the diet with Moringa oleifera extracts to WKY rats did not alter basal [Ca(2+)](i) in T cells but increased basal [Ca(2+)](i) in SHR. Our study clearly demonstrated that Moringa oleifera exerts antihypertensive effects by inhibiting the secretion of IL-2 and modulates T cell calcium signaling in hypertensive rats.

A novel mutation in the succinate dehydrogenase subunit D gene in siblings with the hereditary paraganglioma–pheochromocytoma syndrome

Directory of Open Access Journals (Sweden)

Chaithra Prasad

2014-10-01

Full Text Available Germline mutations in the succinate dehydrogenase complex subunit D gene are now known to be associated with hereditary paraganglioma–pheochromocytoma syndromes. Since the initial succinate dehydrogenase complex subunit D gene mutation was identified about a decade ago, more than 131 unique variants have been reported. We report the case of two siblings presenting with multiple paragangliomas and pheochromocytomas; they were both found to carry a mutation in the succinate dehydrogenase complex subunit D gene involving a substitution of thymine to guanine at nucleotide 236 in exon 3. This particular mutation of the succinate dehydrogenase complex subunit D gene has only been reported in one previous patient in Japan; this is, therefore, the first report of this pathogenic mutation in siblings and the first report of this mutation in North America. With continued screening of more individuals, we will be able to create a robust mutation database that can help us understand disease patterns associated with particular variants and may be a starting point in the development of new therapies for familial paraganglioma syndromes.

Sepsis-induced alteration in T-cell Ca(2+) signaling in neonatal rats.

Science.gov (United States)

Alattar, M H; Ravindranath, T M; Choudhry, M A; Muraskas, J K; Namak, S Y; Dallal, O; Sayeed, M M

2001-01-01

Sepsis-induced suppression in T-cell proliferation follows deranged Ca(2+) signaling in adult rats. In preliminary studies, we observed suppression in T-cell proliferation in septic neonatal rats as well. In this study, we assessed splenic T-cell cytosolic Ca(2+) concentration, [Ca(2+)](i), as its elevation plays an important role in T-cell proliferation. Also, we investigated the role of PGE(2) in sepsis-related changes in T-cell [Ca(2+)](i) in animals pretreated with cyclooxygenase-1 (COX-1) inhibitor (resveratrol) and cyclooxygenase-2 (COX-2) inhibitor (NS-398). Sepsis was induced in 15-day-old rat pups by intraperitoneal implantation of fecal pellets containing Escherichia coli and Bacteroides fragilis. The sham group consisted of pups implanted with sterile fecal pellets. Septic and sham pups were sacrificed 24 h after implantation and their spleens were removed. The spleens from sham and septic pups, along with spleens from unoperated control pups, were processed for single cell suspensions, and T cells were isolated using nylon wool columns. Fura-2 fluorophotometry was employed for the measurement of [Ca(2+)](i) (in nM units) in T cells stimulated with concanavalin A (ConA). Our results show that ConA-mediated T-cell [Ca(2+)](i) response is significantly suppressed in septic neonatal rats. Pretreatment of pups with COX-2, but not COX-1 inhibitor, prevented the decrease in the [Ca(2+)](i) response. These findings suggest that PGE(2) might induce the attenuation in T-cell Ca(2+) signaling during sepsis in neonatal rats. Copyright 2001 S. Karger AG, Basel

Effect of methylmercury on histamine release from rat mast cells

Energy Technology Data Exchange (ETDEWEB)

Graevskaya, Elizabeth E.; Rubin, Andrew B. [Moscow State University, Biological Faculty, Department of Biophysics, 119899, Vorobjovy Gory, Moscow (Russian Federation); Yasutake, Akira; Aramaki, Ryoji [National Institute for Minamata Disease, 4058-18 Hama, Minamata, Kumamoto 867-0008 (Japan)

2003-01-01

Methylmercury chloride (MeHgCl) is well known as a significant environmental hazard, particularly as a modulator of the immune system. As it is acknowledged that the critical effector cells in the host response participating in various biological responses are mast cells, we tried to define the possible contribution of mast cells in the development of methylmercury-evoked effects. We investigated the effects of methylmercury on the rat mast cell degranulation induced by non-immunological stimuli (the selective liberator of histamine, compound 48/80, and calcium ionophore A23187) both in vivo and in vitro. Using the cells prepared from methylmercury-intoxicated rats through a 5-day treatment of MeHgCl (10 mg/kg/day), we observed the suppression of calcium ionophore A23187- and 48/80-induced histamine release, which was enhanced with time after treatment. Similar suppression was observed in the ionophore-stimulated release, when cells were prepared from rat with a single treatment of MeHgCl (20 mg/kg). It should be noted that when cells from the control rat were pre-incubated with methylmercury in vitro at a 10{sup -8} M concentration for 10 min, A23187 and compound 48/80-stimulated histamine release was significantly enhanced. However, when the pre-incubation period was prolonged to 30 min, the release was suppressed. An increase in the methylmercury concentration to 10{sup -6} M also suppressed the histamine release. These results show that methylmercury treatment can modify mast cell function depending on concentration and time, and might provide an insight into the role of mast cells in the development of methylmercury-stimulated effects. (orig.)

Rat primary embryo fibroblast cells suppress transformation by the E6 and E7 genes of human papillomavirus type 16 in somatic hybrid cells.

OpenAIRE

Miyasaka, M; Takami, Y; Inoue, H; Hakura, A

1991-01-01

The E6 and E7 genes of human papillomavirus type 16 (HPV-16) transform established lines of rat cells but not rat cells in primary culture irrespective of the expression of the two genes. The reason for this difference between the susceptibilities of cell lines and primary cells was examined by using hybrid cells obtained by somatic cell fusion of rat cell lines transformed by the E6 and E7 genes of HPV-16 and freshly isolated rat embryo fibroblast cells. In these hybrid cells, transformed ph...

Myenteric denervation differentially reduces enteroendocrine serotonin cell population in rats during postnatal development.

Science.gov (United States)

Hernandes, Luzmarina; Fernandes, Marilda da Cruz; Pereira, Lucieni Cristina Marques da Silva; Freitas, Priscila de; Gama, Patrícia; Alvares, Eliana Parisi

2006-05-01

The enteric nervous and enteroendocrine systems regulate different processes in the small intestine. Ablation of myenteric plexus with benzalkonium chloride (BAC) stimulates epithelial cell proliferation, whereas endocrine serotonin cells may inhibit the process. To evaluate the connection between the systems and the influence of myenteric plexus on serotoninergic cells in rats during postnatal development, the ileal plexus was partially removed with BAC. Rats were treated at 13 or 21 days and sacrificed after 15 days. The cell bodies of myenteric neurons were stained by beta NADH-diaphorase to detect the extension of denervation. The number of enteroendocrine cells in the ileum was estimated in crypts and villi in paraffin sections immunostained for serotonin. The number of neurons was reduced by 27.6 and 45% in rats treated on the 13th and 21st days, respectively. We tried to establish a correlation of denervation and the serotonin population according to the age of treatment. We observed a reduction of immunolabelled cells in the crypts of rats treated at 13 days, whereas this effect was seen in the villi of rats denervated at 21 days. These results suggest that the enteric nervous system might control the enteroendocrine cell population and this complex mechanism could be correlated to changes in cell proliferation.

A Somatic HIF2α Mutation-Induced Multiple and Recurrent Pheochromocytoma/Paraganglioma with Polycythemia: Clinical Study with Literature Review.

Science.gov (United States)

Liu, Qiuli; Wang, Yan; Tong, Dali; Liu, Gaolei; Yuan, Wenqiang; Zhang, Jun; Ye, Jin; Zhang, Yao; Yuan, Gang; Feng, Qingxing; Zhang, Dianzheng; Jiang, Jun

2017-03-01

A syndrome known as pheochromocytomas (PCC)/paragangliomas (PGL) and polycythemia resulted from gain-of-function mutation of hypoxia-inducible factor 2α (HIF2α) has been reported recently. However, clinical features of this syndrome vary from patient to patient. In our study, we described the clinical features of the patient within 15-year follow-up with a literature review. The patient presented with "red face" since childhood and was diagnosed with polycythemia and pheochromocytoma in 2000, and then, tumor was removed at his age of 27 (year 2000). However, 13 years later (2013), he was diagnosed with multiple paragangliomas. Moreover, 2 years later (2015), another two paragangaliomas were also confirmed. Genetic analysis of hereditary PCC/PGL-related genes was conducted. A somatic heterozygous missense mutation of HIF2α (c.1589C>T) was identified at exon 12, which is responsible for the elevated levels of HIF2α and erythropoietin (EPO) and subsequent development of paragangaliomas. However, this mutation was only found in the tumors from three different areas, not in the blood. So far, 13 cases of PCC/PGL with polycythemia have been reported. Among them, somatic mutations of HIF2α at exon 12 are responsible for 12 cases, and only 1 case was caused by germline mutation of HIF2α at exon 9. The HIF2α mutation-induced polycythemia with PCC/PGL is a rare syndrome with no treatment for cure. Comprehensive therapies for this disease include removal of the tumors and intermittent phlebotomies; administration of medications to control blood pressure and to prevent complications or death resulted from high concentration of red blood cell (RBC). Genetic test is strongly recommended for patients with early onset of polycythemia and multiple/recurrent PCC/PGL.

Novel use of F-DOPA PET/CT imaging in a child with paraganglioma/pheochromocytoma syndrome

International Nuclear Information System (INIS)

Levine, Daniel S.; Nadel, Helen R.; Metzger, Daniel L.; Oviedo, Angelica; Adam, Michael J.; Skarsgard, Erik

2011-01-01

We report the use of F-DOPA PET/CT imaging in the evaluation of a teenager with marked hypertension and right pararenal, left adrenal and left para-aortic mass lesions. The use of the modality for this clinical application has not been described previously within the pediatric imaging literature. The value of this technique relative to conventional imaging modalities is discussed and warrants consideration of its use, if available, for evaluating children with suspected paragangliomas/pheochromocytomas. (orig.)

Novel use of F-DOPA PET/CT imaging in a child with paraganglioma/pheochromocytoma syndrome

Energy Technology Data Exchange (ETDEWEB)

Levine, Daniel S.; Nadel, Helen R. [University of British Columbia, Department of Radiology and Nuclear Medicine, British Columbia Children' s Hospital, Vancouver (Canada); Metzger, Daniel L. [University of British Columbia, Department of Pediatrics, Division of Endocrinology, British Columbia Children' s Hospital, Vancouver (Canada); Oviedo, Angelica [University of British Columbia, Department of Pathology, British Columbia Children' s Hospital, Vancouver (Canada); Adam, Michael J. [University of British Columbia, Department of PET Chemistry, Tri-University Meson Facility (TRIUMF), Vancouver (Canada); Skarsgard, Erik [University of British Columbia, Department of Surgery, British Columbia Children' s Hospital, Vancouver (Canada)

2011-10-15

We report the use of F-DOPA PET/CT imaging in the evaluation of a teenager with marked hypertension and right pararenal, left adrenal and left para-aortic mass lesions. The use of the modality for this clinical application has not been described previously within the pediatric imaging literature. The value of this technique relative to conventional imaging modalities is discussed and warrants consideration of its use, if available, for evaluating children with suspected paragangliomas/pheochromocytomas. (orig.)

Tuning differentiation signals for efficient propagation and in vitro validation of rat embryonic stem cell cultures.

Science.gov (United States)

Meek, Stephen; Sutherland, Linda; Burdon, Tom

2015-01-01

The rat is one of the most commonly used laboratory animals in biomedical research and the recent isolation of genuine pluripotent rat embryonic stem (ES) cell lines has provided new opportunities for applying contemporary genetic engineering techniques to the rat and enhancing the use of this rodent in scientific research. Technical refinements that improve the stability of the rat ES cell cultures will undoubtedly further strengthen and broaden the use of these stem cells in biomedical research. Here, we describe a relatively simple and robust protocol that supports the propagation of germ line competent rat ES cells, and outline how tuning stem cell signaling using small molecule inhibitors can be used to both stabilize self-renewal of rat ES cell cultures and aid evaluation of their differentiation potential in vitro.

Malignant pheochromocytomas and paragangliomas - the importance of a multidisciplinary approach

DEFF Research Database (Denmark)

Andersen, Kim Francis; Altaf, Rahim; Krarup-Hansen, Anders

2011-01-01

-secreted with catecholamines, may indicate tumour mass and malignancy and can be used to monitor response and relapse. The secretory and non-secretory tumours can be visualised with functional (specific and non-specific) imaging as SPECT and PET using ¹²³I-MIBG, somatostatin analogues, ¹8F-DOPA, and ¹8F-FDG. These modalities...... imaging with somatostatin analogues generally has high sensitivity in malignant disease. There are no curative therapeutic options for malignant, metastatic pheochromocytomas/paragangliomas, wherefore consolidation of quality of life is essential. Adjuvant radionuclide treatment with beta......-emitting isotopes coupled to MIBG or somatostatin analogues have shown response in approximately 30%. Chemotherapy is restricted to patients not accessible for surgery and resistant to radionuclide therapy. Novel targeted therapies, which mainly through a cytostatic effect interfere with specific targeted molecules...

Cell apoptosis of taste buds in circumvallate papillae in diabetic rats.

Science.gov (United States)

Cheng, B; Pan, S; Liu, X; Zhang, S; Sun, X

2011-09-01

Diabetes mellitus may result in taste disturbance. The present study has revealed that cell apoptosis of taste buds in circumvallate papillae may contribute to the taste disturbance in a rat model of type2 diabetes. Type2 diabetes was induced in Wistar rats by feeding them with a high-fat diet (30% fat), and a single intraperitoneal injection of streptozotocin (30 mg/kg). The increased cell apoptosis of taste buds in circumvallate papilla sections was detected by TUNEL staining in diabetic rats, and the ultrastructure was further examined by transmission electronic microscopy. Immunohistochemical and Western blot analyses revealed the downregulation of Bcl-2, upregulation of Bax, and increased activation of caspase-9 and -3, in diabetic rats, indicating that the apoptosis of taste bud cells may be mediated via the intrinsic mitochondrial pathway in diabetics. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.

Birth of rats following nuclear exchange at the 2-cell stage.

Science.gov (United States)

Roh, Sangho; Guo, Jitong; Malakooti, Nakisa; Morrison, John R; Trounson, Alan O; Du, Zhong Tao

2003-11-01

We report full-term development of nuclear transfer embryos following nuclear exchange at the 2-cell stage. Nuclei from 2-cell rat embryos were transferred into enucleated 2-cell embryos and developed to term after transfer to recipients (NT2). Pronuclear exchange in zygotes was used for comparison (NT1). Zygotes and 2-cell embryos were harvested from 4-week-old female Sprague-Dawley rats. Nuclear transfer was performed by transferring the pronuclei or karyoplasts into the perivitelline space of recipient embryos followed by electrofusion to reconstruct embryos. Fused couplets were cultured for 4 or 24 h before being transferred into day 1 pseudopregnant recipients (Hooded Wistar) at the 1- or 2-cell stage. In vitro culture was also carried out to check the developmental competence of the embryos. In vitro development to the blastocyst stage was not significantly different between the two groups (NT1, 34.3%; NT2, 45.0%). Two of three recipients from NT1 and two of five recipients from NT2 became pregnant. Six pups (3 from NT1, 3 from NT2) were delivered from the four foster mothers. Three female pups survived; 2 from NT1 and 1 from NT2. At 2 months of age these pups appeared healthy, and were mated with Sprague-Dawley males. One rat derived from NT1 delivered 15 pups (5 males, 10 females) as did the rat from NT2 (7 males, 8 females). Our results show that by using karyoplasts from 2-cell stage embryos as nuclear donors and reconstructing them with enucleated 2-cell embryos, healthy rats can be produced.

Mangosteen peel extract reduces formalin-induced liver cell death in rats

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Afiana Rohmani

2014-08-01

Full Text Available Background Formalin is a xenobiotic that is now commonly used as a preservative in the food industry. The liver is an organ that has the highest metabolic capacity as compared to other organs. Mangosteen or Garcinia mangostana Linn (GML peel contains xanthones, which are a source of natural antioxidants. The purpose of this study was to evaluate the effect of mangosteen peel extract on formalin-induced liver cell mortality rate and p53 protein expression in Wistar rats. Methods Eighteen rats received formalin orally for 2 weeks, and were subsequently divided into 3 groups, consisting of the formalin-control group receiving a placebo and treatment groups 1 and 2, which were treated with mangosteen peel extract at doses of 200 and 400 mg/kgBW/day, respectively. The treatment was carried out for 1 week, and finally the rats were terminated. The differences in liver cell mortality rate and p53 protein expression were analyzed. Results One-way ANOVA analysis showed significant differences in liver cell mortality rate among the three groups (p=0.004. The liver cell mortality rate in the treatment group receiving 400 mg/kgBW/day extract was lower than that in the formalin-control group. There was no p53 expression in all groups. Conclusions Garcinia mangostana Linn peel extract reduced the mortality rate of liver cells in rats receiving oral formalin. Involvement of p53 expression in liver cell mortality in rats exposed to oral formalin is presumably negligible.

Efficient generation of rat induced pluripotent stem cells using a non-viral inducible vector.

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Claudia Merkl

Full Text Available Current methods of generating rat induced pluripotent stem cells are based on viral transduction of pluripotency inducing genes (Oct4, Sox2, c-myc and Klf4 into somatic cells. These activate endogenous pluripotency genes and reprogram the identity of the cell to an undifferentiated state. Epigenetic silencing of exogenous genes has to occur to allow normal iPS cell differentiation. To gain more control over the expression of exogenous reprogramming factors, we used a novel doxycycline-inducible plasmid vector encoding Oct4, Sox2, c-Myc and Klf4. To ensure efficient and controlled generation of iPS cells by plasmid transfection we equipped the reprogramming vector with a bacteriophage φC31 attB site and used a φC31 integrase expression vector to enhance vector integration. A series of doxycycline-independent rat iPS cell lines were established. These were characterized by immunocytochemical detection of Oct4, SSEA1 and SSEA4, alkaline phosphatase staining, methylation analysis of the endogenous Oct4 promoter and RT-PCR analysis of endogenous rat pluripotency genes. We also determined the number of vector integrations and the extent to which reprogramming factor gene expression was controlled. Protocols were developed to generate embryoid bodies and rat iPS cells demonstrated as pluripotent by generating derivatives of all three embryonic germ layers in vitro, and teratoma formation in vivo. All data suggest that our rat iPS cells, generated by plasmid based reprogramming, are similar to rat ES cells. Methods of DNA transfection, protein transduction and feeder-free monolayer culture of rat iPS cells were established to enable future applications.

Preservation of photoreceptors in dystrophic RCS rats following allo- and xenotransplantation of IPE cells.

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Thumann, Gabriele; Salz, Anna Katharina; Walter, Peter; Johnen, Sandra

2009-03-01

To examine whether iris pigment epithelial (IPE) cells transplanted into the subretinal space of Royal College of Surgeons (RCS) rats have the ability to rescue photoreceptors. Rat IPE (rIPE) or human IPE (hIPE) cells were transplanted subretinally in 23-day-old RCS rats. Sham injection and transplantation of ARPE-19 cells served as controls. After 12 weeks, eyes were evaluated for photoreceptor survival by morphometric analysis and electron microscopy. Morphometric analysis showed photoreceptor rescue in all transplanted and sham-injected animals (number of photoreceptors/300 microm retina+/-sd: rIPE 41.67 +/- 28; hIPE 29.50 +/- 16; ARPE-19 36.12 +/- 21; sham 16.56 +/- 6) compared to age-matched, control rats (number of photoreceptors/300 microm retina+/-sd: 9.71 +/- 4). Photoreceptor rescue was prominent in IPE cell-transplanted rats and was significantly greater than sham-injected eyes (p = 0.02 for rIPE and p = 0.04 for hIPE). Since IPE cells transplanted into the subretinal space have the ability to rescue photoreceptors from degeneration in the RCS rat without any harmful effects, IPE cells may represent an ideal cell to genetically modify and thus carry essential genetic information for the repair of defects in the subretinal space.

Cell proliferation and migration in the jejunum of suckling rats submitted to progressive fasting

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Gomes J.R.

1998-01-01

Full Text Available Cell proliferation and migration in the intestinal crypts, and cell migration in the villus are controlled by different mechanisms in adult rats. In the present study, weanling rats and fasting rats were used to quantitatively study the correlation of cell cycle parameters and epithelial cell migration in crypts and intestinal villi. Eighteen-day-old rats received a single injection of tritiated thymidine [3H]TdR (23:00 h; half of the pups were submitted to fasting 5 h earlier. Cell proliferation was determined in radioautographs of jejunal crypts, on the basis of the labeling indices (LI taken 1, 8, 13 and 19 h after [3H]TdR. The results showed that the labeling index did not differ 1 h or 19 h after [3H]TdR between the fed (38.7% or 48% and fasting groups (34.6% or 50.4%. The modified method of grain count halving indicated that cell cycle time did not differ between fed (16.5 h and fasting rats (17.8 h; the growth fraction, however, had lower values in fasting (59% than in fed rats (77%. Cell migration in the crypt, estimated by the LI obtained for each cell position, did not change with treatment. As for the villi, the cell migration rate was significantly retarded by 3 cell positions (8%. These results suggest that the cell migration in the villi of weanling pups does not depend directly on the cell proliferation and migration in the intestinal crypt, but is directly affected by the absence of food in the lumen

Intraportal injection of insulin-producing cells generated from human bone marrow mesenchymal stem cells decreases blood glucose level in diabetic rats.

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Tsai, Pei-Jiun; Wang, Hwai-Shi; Lin, Chi-Hung; Weng, Zen-Chung; Chen, Tien-Hua; Shyu, Jia-Fwu

2014-01-01

We studied the process of trans-differentiation of human bone marrow mesenchymal stem cells (hBM-MSCs) into insulin-producing cells. Streptozotocin (STZ)-induced diabetic rat model was used to study the effect of portal vein transplantation of these insulin-producing cells on blood sugar levels. The BM-MSCs were differentiated into insulin-producing cells under defined conditions. Real-time PCR, immunocytochemistry and glucose challenge were used to evaluate in vitro differentiation. Flow cytometry showed that hBM-MSCs were strongly positive for CD44, CD105 and CD73 and negative for hematopoietic markers CD34, CD38 and CD45. Differentiated cells expressed C-peptide as well as β-cells specific genes and hormones. Glucose stimulation increased C-peptide secretion in these cells. The insulin-producing, differentiated cells were transplanted into the portal vein of STZ-induced diabetic rats using a Port-A catheter. The insulin-producing cells were localized in the liver of the recipient rat and expressed human C-peptide. Blood glucose levels were reduced in diabetic rats transplanted with insulin-producing cells. We concluded that hBM-MSCs could be trans-differentiated into insulin-producing cells in vitro. Portal vein transplantation of insulin-producing cells alleviated hyperglycemia in diabetic rats.

Bronchoalveolar lavage fluid from normal rats stimulates DNA synthesis in rat alveolar type II cells

International Nuclear Information System (INIS)

Leslie, C.C.; McCormick-Shannon, K.; Mason, R.J.

1989-01-01

Proliferation of alveolar type II cells after lung injury is important for the restoration of the alveolar epithelium. Bronchoalveolar lavage fluid (BALF) may represent an important source of growth factors for alveolar type II cells. To test this possibility, BALF fluid was collected from normal rats, concentrated 10-fold by Amicon filtration, and tested for its ability to stimulate DNA synthesis in rat alveolar type II cells in primary culture. BALF induced a dose-dependent increase in type II cell DNA synthesis resulting in a 6-fold increase in [3H]thymidine incorporation. Similar doses also stimulated [3H]thymidine incorporation into rat lung fibroblasts by 6- to 8-fold. Removal of pulmonary surface active material by centrifugation did not significantly reduce the stimulatory activity of BALF for type II cells. The stimulation of type II cell DNA synthesis by BALF was reduced by 100% after heating at 100 degrees C for 10 min, and by approximately 80% after reduction with dithiothreitol, and after trypsin treatment. Dialysis of BALF against 1 N acetic acid resulted in a 27% reduction in stimulatory activity. The effect of BALF in promoting type II cell DNA synthesis was more pronounced when tested in the presence of serum, although serum itself has very little effect on type II cell DNA synthesis. When BALF was tested in combination with other substances that stimulate type II cell DNA synthesis (cholera toxin, insulin, epidermal growth factor, and acidic fibroblast growth factor), additive effects or greater were observed. When BALF was chromatographed over Sephadex G150, the activity eluted with an apparent molecular weight of 100 kDa

[In vitro generation of insulin-producing cells from the neonatal rat bone marrow mesenchymal stem cells].

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Li, Xiaohu; Huang, Haiyan; Liu, Xirong; Xia, Hongxia; Li, Mincai

2015-03-01

To observe the differentiation of the neonatal rat bone marrow mesenchymal stem cells (MSCs) into insulin-producing cells and detect the expressions of insulin, pancreatic duodenal homebox-1 (PDX-1) and nestin. MSCs were isolated from the neonatal rats and cultured in the modified medium composed of 10 μg/L human epidermal growth factor (EGF), 10 μg/L basic fibroblast growth factor (bFGF), 10 μg/L hepatocyte growth factor (HGF), 10 μg/L human B cell regulin, 20 mmol/L nicotinamide and 20 g/L B27. After the induction, the mRNA expressions of insulin, PDX-1 and nestin were examined by reverse transcription-PCR, and the insulin, PDX-1 and nestin protein levels were detected by immunocytochemistry. The insulin and PDX-1 mRNA expressions increased and the nestin mRNA expression decreased in the differentiation of the neonatal rat MSCs into insulin-producing cells. The nestin, PDX-1 and insulin proteins were co-expressed in insulin-producing cells. MSCs can be induced to differentiate into insulin-producing cells.

Effects of X-irradiation on glial cells in the developing rat brain

International Nuclear Information System (INIS)

Ferrer, I.; Borras, D.

1994-01-01

Sprague-Dawley rats were given a single dose of 2Gy X-rays when 1 or 3 days of age. Dying cells in the germinal layer of the telencephalon reached peak values 6h after irradiation; dead cells were cleared 48h later. These effects were almost abolished with the injection of cyclohexamide (1 μg/g body weight) given at the time of irradiation. PCNA-immunoreactive cells (cells in late G 1 and S phases of the cell cycle) and PCNA-negative cells were sensitive to X-rays. Long-term effects on glial cell populations in the subcortical white matter of the cingulum were examined in irradiated rats, killed at postnatal day 30 (P30), by means of glial fibrillary acidic protein, vimentin and S-100 immunohistochemistry, as well as with anti-TGF-α (transformerly growth factor) antibodies that are used as putative oligodendrogial cell markers in the white matter of rat. (author)

Fibroblast-mediated in vivo and in vitro growth promotion of tumorigenic rat thyroid carcinoma cells but not normal Fisher rat thyroid follicular cells.

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Saitoh, Ohki; Mitsutake, Norisato; Nakayama, Toshiyuki; Nagayama, Yuji

2009-07-01

It is known that genetic abnormalities in oncogenes and/or tumor suppressor genes promote carcinogenesis. Numerous recent articles, however, have demonstrated that epithelial-stromal interaction also plays a critical role for initiation and progression of carcinoma cells. Furthermore, ionizing radiation induces alterations in the tissue microenvironments that promote carcinogenesis. There is little or no information on epithelial-stromal interaction in thyroid carcinoma cells. The objective of this study was to determine if epithelial-stromal interaction influenced the growth of thyroid carcinoma cells in vivo and in vitro and to determine if radiation had added or interacting effects. Normal Fisher rat thyroid follicular cells (FRTL5 cells) and tumorigenic rat thyroid carcinoma cells (FRTL-Tc cells) derived from FRTL5 cells were employed. The cells were injected into thyroids or subcutaneously into left flanks of rats alone or in combination with skin-derived fibroblasts. In groups of rats, fibroblasts were irradiated with 0.1 or 4 Gy x-ray 3 days before inoculation. In vitro growth of FRTL-Tc and FRTL-5 cells were evaluated using the fibroblast-conditioned medium and in a co-culture system with fibroblasts. The in vivo experiments demonstrated that FRTL-Tc cells injected intrathyroidally grew faster than those injected subcutaneously, and that admixed fibroblasts enhanced growth of subcutaneous FRTL-Tc tumors, indicating that the intrathyroidal milieu, particularly in the presence of fibroblasts, confer growth-promoting advantage to thyroid carcinoma cells. This in vivo growth-promoting effect of fibroblasts on FRTL-Tc cells was duplicated in the in vitro experiments using the fibroblast-conditioned medium. Thus, our data demonstrate that this effect is mediated by soluble factor(s), is reversible, and is comparable to that of 10% fetal bovine serum. However, normal FRTL5 cells did not respond to the fibroblast-conditioned medium. Furthermore, high- and low

Feocromocitoma. Presentación de un caso clínico. Pheochromocytoma. A clinical case report.

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Maité Cabrera Gámez

2008-08-01

Full Text Available El feocromocitoma es un tumor de células cromafines, que puede localizarse en los territorios derivados de la cresta neural, o en el trayecto que siguen estas células hasta su localización definitiva. Por lo general se ubican en el abdomen (90 % de los casos particularmente en las glándulas suprarrenales y en el órgano de Zuckerkandl. Pueden causar una amplia variedad de síntomas, dada su capacidad de secretar catecolaminas, particularmente noradrenalina y adrenalina, en cantidades variables e intermitentes. Clínicamente pueden ser asintomáticos o presentarse con hipertensión arterial paroxística, o permanente con o sin paroxismos, acompañados de la triada clásica de cefalea, hiperhidrosis y taquicardia. Teniendo en cuenta lo anterior decidimos presentar un caso clínico de un paciente de sexo masculino, de 40 años de edad, con antecedentes de hipertensión arterial controlada, aparentemente de tipo esencial de varios años de evolución, con el diagnóstico de tumoración suprarrenal derecha incidental, aparentemente no funcionante, y que después de la palpación abdominal pre-quirúrgica, comienza con una crisis paroxística hipertensiva severa. Se prepara con alfa bloqueador y se interviene con informe anatomopatológico de feocromocitoma de suprarrenal derecha.The pheochromocytoma is a tumor of the chromaffin cells that may be located in territories derived from the neural crest or in the way these cells follow to their definitive localization. Generally, they are located in the abdomen (90 % of the cases, particularly in the suprarenal glands and in Zuckerkandl's organ. They may cause a wide variety of symptoms due to their capacity for secreting catecholamine, specifically noradrenalin and adrenaline in variable and intermittent amounts. Clinically, they may be asymptomatic or appear with paroxistic arterial hypertension, or permanent with or without paroxisms, accompanied with the classic triad of headache, hyperhydrosis and

Comparative study of muscarinic acetylcholine receptors of human and rat cortical glial cells

International Nuclear Information System (INIS)

Demushkin, V.P.; Burbaeva, G.S.; Dzhaliashvili, T.A.; Plyashkevich, Y.G.

1985-01-01

The aim of the present investigation was a comparative studyof muscarinic acetylcholine receptors in human and rat glial cells. ( 3 H)Quinuclidinyl-benzylate (( 3 H)-QB), atropine, platiphylline, decamethonium, carbamylcholine, tubocurarine, and nicotine were used. The glial cell fraction was obtained from the cerebral cortex of rats weighing 130-140 g and from the frontal pole of the postmortem brain from men aged 60-70 years. The use of the method of radioimmune binding of ( 3 H)-QB with human and rat glial cell membranes demonstrated the presence of a muscarinic acetylcholine receptor in the glial cells

Postirradiation recovery of lymphoid cells in the rat

International Nuclear Information System (INIS)

Farnsworth, A.; Wotherspoon, J.S.; Dorsch, S.E.

1988-01-01

Whole-body irradiation has been extensively used to remove immune responsiveness in rodent recipients in adoptive allograft assays. This study was undertaken to determine the relative radioresistance and the tempo of regeneration, following whole-body irradiation, of cells involved in the allograft response. Six distinct cell populations have been identified in the lymphoid tissues of rats subjected to sublethal whole-body irradiation. The relative representation of these subpopulations was significantly different from that in nonirradiated controls. NK cells, macrophages, and plasma cells, which are present in very low numbers in cell suspensions prepared from normal lymphoid tissues, made up a significant proportion of the residual/regenerating population in the tissues of rats recovering from whole-body irradiation. More significantly perhaps, the mature T cell populations showed a significant increase in the T cytotoxic/suppressor to T helper cell ratio. These observations support the suggestion that a number of the cell types within the mixed cell population observed in the rejecting indicator grafts of irradiated recipients in adoptive allograft assays are host derived. The finding that the T cytotoxic/suppressor population is apparently more radioresistant than the T helper population supports a conclusion that graft rejection in irradiated recipients, restored with pure populations of T helper cells, may not be directly mediated by the injected cells but may be the result of collaboration between these and host-derived cytotoxic cell populations

The volume of Purkinje cells decreases in the cerebellum of acrylamide-intoxicated rats, but no cells are lost

DEFF Research Database (Denmark)

Larsen, Jytte Overgaard; Tandrup, T; Braendgaard, H

1994-01-01

The effects of acrylamide intoxication on the numbers of granule and Purkinje cells and the volume of Purkinje cell perikarya have been evaluated with stereological methods. The analysis was carried out in the cerebella of rats that had received a dose of 33.3 mg/kg acrylamide, twice a week, for 7.......5 weeks. The total numbers of cerebellar granule and Purkinje cells were estimated using the optical fractionator and the mean volume of the Purkinje cell perikarya was estimated with the vertical rotator technique. The volumes of the molecular layer, the granular cell layer and the white matter were...... estimated using the Cavalieri principle. The mean weight of the cerebellum of the intoxicated rats was 7% lower than that of the control rats (2P = 0.001). The numbers of the Purkinje cells and granule cells were the same in both groups, but the mean volume of the perikarya of the Purkinje cells...

Experimental induction of ovarian Sertoli cell tumors in rats by N-nitrosoureas.

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Maekawa, A; Onodera, H; Tanigawa, H; Furuta, K; Kanno, J; Ogiu, T; Hayashi, Y

1987-01-01

Spontaneous ovarian tumors are very rare in ACI, Wistar, F344 and Donryu rats; the few neoplasms found are of the granulosa/theca cell type. Ovarian tumors were also rare in these strains of rats when given high doses of N-alkyl-N-nitrosoureas continuously in the drinking water for their life-span; however, relatively high incidences of Sertoli cell tumors or Sertoli cell tumors mixed with granulosa cell tumors were induced in Donryu rats after administration of either a 400 ppm N-ethyl-N-nitrosourea solution in the drinking water for 4 weeks or as a single dose of 200 mg N-propyl-N-nitrosourea per kg body weight by stomach tube. Typical Sertoli cell tumors consisted of solid areas showing tubular formation. The tubules were lined by tall, columnar cells, with abundant, faintly eosinophilic, often vacuolated cytoplasm, and basally oriented, round nuclei, resembling seminiferous tubules in the testes. In some cases, Sertoli cell tumor elements were found mixed with areas of granulosa cells. The induction of ovarian Sertoli cell tumors in Donryu rats by low doses of nitrosoureas may provide a useful model for these tumors in man. Images PLATE 1. PLATE 2. PLATE 3. PLATE 4. PLATE 5. PLATE 6. PLATE 7. PLATE 8. PLATE 9. PLATE 10. PLATE 11. PLATE 12. PLATE 13. PLATE 14. PLATE 15. PLATE 16. PMID:3665856

Heterogeneity within the spleen colony-forming cell population in rat bone marrow

International Nuclear Information System (INIS)

Martens, A.C.; van Bekkum, D.W.; Hagenbeek, A.

1986-01-01

The pluripotent hemopoietic stem cell (HSC) of the rat can be enumerated in a spleen colony assay (SCA) in rats as well as mice. After injection of rat bone marrow into lethally irradiated mice, macroscopically visible spleen colonies (CFU-S) are found from day 6 through 14, but the number varies on consecutive days. In normal bone marrow a constant ratio of day-8 to day-12 colony numbers is observed. However, this ratio is changed after in vivo treatment of rats with cyclophosphamide, as well as after in vitro treatment of rat bone marrow with cyclophosphamide derivatives. This indicates that the CFU-S that form colonies on day 8 react differently to this treatment than the CFU-S that form colonies on day 12, and suggests heterogeneity among the CFU-S population. Posttreatment regrowth of day-8 and day-12 CFU-S is characterized by differences in population-doubling times (Td = 0.85 days vs 1.65 days). Another argument in support of the postulate of heterogeneity within the rat CFU-S population is derived from the fact that (in contrast to normal rat spleen) the spleen of leukemic rats contains high numbers of CFU-S that show a ratio of day-8 to day-12 CFU-S of 4.5, which is different than that observed for a CFU-S population in normal bone marrow (a ratio of 2.4). It is concluded that, in rat hemopoiesis, two populations of spleen colony-forming cells can be distinguished using the rat-to-mouse SCA. This indicates that mouse and rat hemopoiesis are comparable in this respect and that heterogeneity in the stem cell compartment is a general phenomenon

Erythroid differentiation and commitment in rat erythroleukemia cells with hypertonic culture conditions.

OpenAIRE

Yamaguchi, Y; Kluge, N; Ostertag, W; Furusawa, M

1981-01-01

Cell cultures of 7,12-dimethylbenz[a]anthracene-induced rat erythroleukemia can be stimulated to synthesize hemoglobin when cultured in hypertonic media. During hypertonic treatment the intracellular osmotic conditions immediately readjust to those of the extracellular medium. None of the Friend virus-induced mouse erythroleukemia cell lines was inducible for differentiation with the same hypertonic culture conditions used for rat cells. Earliest commitment to erythroid terminal differentiati...

Use of rat mature adipocyte-derived dedifferentiated fat cells as a cell source for periodontal tissue regeneration

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Daisuke eAkita

2016-02-01

Full Text Available Lipid-free fibroblast-like cells, known as dedifferentiated fat (DFAT cells, can be generated from mature adipocytes with a large single lipid droplet. DFAT cells can re-establish their active proliferation ability and can transdifferentiate into various cell types under appropriate culture conditions. The first objective of this study was to compare the multilineage differentiation potential of DFAT cells with that of adipose-derived stem cells (ASCs on mesenchymal stem cellsWe obtained DFAT cells and ASCs from inbred rats and found that rat DFAT cells possess higher osteogenic differentiation potential than rat ASCs. On the other hand, DFAT cells show similar adipogenic differentiation, and chondrogenic differentiation potential in comparison with ASCs. The second objective of this study was to assess the regenerative potential of DFAT cells combined with novel solid scaffolds composed of PLGA (Poly d, l-lactic-co-glycolic acid on periodontal tissue, and to compare this with the regenerative potential of ASCs combined with PLGA scaffolds. Cultured DFAT cells and ASCs were seeded onto PLGA scaffolds (DFAT/PLGA and ASCs/PLGA and transplanted into periodontal fenestration defects in rat mandible. Micro computed tomography analysis revealed a significantly higher amount of bone regeneration in the DFAT/PLGA group compared with that of ASCs/PLGA and PLGA-alone groups at 2, 3 and 5 weeks after transplantation. Similarly, histomorphometric analysis showed that DFAT/PLGA groups had significantly greater width of cementum, periodontal ligament and alveolar bone than ASCs/PLGA and PLGA-alone groups. In addition, transplanted fluorescent-labeled DFAT cells were observed in the periodontal ligament beside the newly formed bone and cementum. These findings suggest that DFAT cells have a greater potential for enhancing periodontal tissue regeneration than ASCs. Therefore, DFAT cells are a promising cell source for periodontium regeneration.

Isolation, culture and intraportal transplantation of rat marrow stromal cell

International Nuclear Information System (INIS)

Wang Ping; Wang Jianhua; Yan Zhiping; Li Wentao; Lin Genlai; Hu Meiyu; Wang Yanhong

2004-01-01

Objective: To observe the tracing and evolution of marrow stromal cell (MSC) after intraportal transplantation into the liver of homogenous rats, and to provide experimental data for MSC differentiation to hepatocyte in vivo. Methods: The MSC was isolated from the leg bone marrow of adult SD rats, and purified by culture-expanded in vitro. Before transplantation, MSC was labeled with DAPI. Then 10 5 MSC were intraportally transplanted into the homogenous rat liver. Rats were killed at 2 hours and 1, 2, 3 and 4 weeks after transplantation. The cryosection samples of liver and lung were observed under fluorescence microscopy. Results: MSC in vitro culture had high ability of proliferation. Except 4 rats were dead because of abdominal bleeding or infection, other recipients were healthy until sacrificed. The implantation cells were detected by identifying the DAPI labeled MSC in the host livers, but not in the host lungs. Conclusion: Intraportal transplanted MSC could immigrate and survive in the host livers at least for 4 weeks. They could immigrate from the small branches of portal veins to hepatic parenchyma

Does injection of metanephric mesenchymal cells improve renal function in rats?

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Yu-qing Jiao

2011-01-01

Full Text Available Chronic kidney disease (CKD is a massive global health-care problem. Cell therapy offers a potential treatment for CKD. The aim of this study was to investigate whether the administration of a population of stem cells could be used to treat adriamycin (ADR-induced glomerulopathy in rats, a form of CKD. We intravenously transplanted metanephric mesenchymal cells (MMCs into rats treated with ADR. We also induced MMC differentiation in vitro using a medium derived from serum and homogenates of ADR-induced glomerulopathy rats. We detected the induction of an early epithelial phenotype (cytokeratin-18 expression and a proximal tubule phenotype (vitamin D receptor expression in vitro, and MMC-derived epithelial cells corresponding to the proximal tubule and glomeruli in vivo. Transplantation of MMCs after induction of glomerulopathy significantly increased the creatinine clearance rate (Ccr, a marker for glomerular filtration rate, but had no significant effect on other parameters (24-hour urinary protein excretion, serum albumin, total cholesterol. In addition, there was no significant difference in blood urea nitrogen or serum creatinine levels in rats with and without ADR administration. Our results indicate that MMCs might survive, engraft and differentiate into renal epithelia in vivo when transplanted into ADR-treated rats. However, further studies are needed to determine whether MMC transplantation improves renal function and causes renal repair in this model.

Effects of sciatic-conditioned medium on neonatal rat retinal cells in vitro

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Torres P.M.M.

1998-01-01

Full Text Available Schwann cells produce and release trophic factors that induce the regeneration and survival of neurons following lesions in the peripheral nerves. In the present study we examined the in vitro ability of developing rat retinal cells to respond to factors released from fragments of sciatic nerve. Treatment of neonatal rat retinal cells with sciatic-conditioned medium (SCM for 48 h induced an increase of 92.5 ± 8.8% (N = 7 for each group in the amount of total protein. SCM increased cell adhesion, neuronal survival and glial cell proliferation as evaluated by morphological criteria. This effect was completely blocked by 2.5 µM chelerythrine chloride, an inhibitor of protein kinase C (PKC. These data indicate that PKC activation is involved in the effect of SCM on retinal cells and demonstrate that fragments of sciatic nerve release trophic factors having a remarkable effect on neonatal rat retinal cells in culture.

Positive effects of bFGF modified rat amniotic epithelial cells transplantation on transected rat optic nerve.

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Jia-Xin Xie

Full Text Available Effective therapy for visual loss caused by optic nerve injury or diseases has not been achieved even though the optic nerve has the regeneration potential after injury. This study was designed to modify amniotic epithelial cells (AECs with basic fibroblast growth factor (bFGF gene, preliminarily investigating its effect on transected optic nerve.A human bFGF gene segment was delivered into rat AECs (AECs/hbFGF by lentiviral vector, and the gene expression was examined by RT-PCR and ELISA. The AECs/hbFGF and untransfected rat AECs were transplanted into the transected site of the rat optic nerve. At 28 days post transplantation, the survival and migration of the transplanted cells was observed by tracking labeled cells; meanwhile retinal ganglion cells (RGCs were observed and counted by employing biotin dextran amine (BDA and Nissl staining. Furthermore, the expression of growth associated protein 43 (GAP-43 within the injury site was examined with immunohistochemical staining.The AECs/hbFGF was proven to express bFGF gene and secrete bFGF peptide. Both AECs/hbFGF and AECs could survive and migrate after transplantation. RGCs counting implicated that RGCs numbers of the cell transplantation groups were significantly higher than that of the control group, and the AECs/hbFGF group was significantly higher than that of the AECs group. Moreover GAP-43 integral optical density value in the control group was significantly lower than that of the cell transplantation groups, and the value in the AECs/hbFGF group was significantly higher than that of the AECs group.AECs modified with bFGF could reduce RGCs loss and promote expression of GAP-43 in the rat optic nerve transected model, facilitating the process of neural restoration following injury.

Fraction from human and rat liver which is inhibitory for proliferation of liver cells.

Science.gov (United States)

Chen, T S; Ottenweller, J; Luke, A; Santos, S; Keeting, P; Cuy, R; Lea, M A

1989-01-01

A comparative study was undertaken with human and rat liver of a fraction reported to have growth inhibitory activity when prepared from rat liver. Fractions which were soluble in 70% ethanol and insoluble in 87% ethanol were prepared from liver cytosols. Electrophoretic analysis under denaturing conditions indicated that there were several quantitative or qualitative differences in the fractions from the two species. Fractions from both human and rat liver were found to be inhibitory for the incorporation of 3H-thymidine into DNA of foetal chick hepatocytes. Under conditions in which the rat fraction inhibited precursor incorporation into DNA of rat liver epithelial cells there was not a significant inhibitory effect with the fraction from human liver. DNA synthesis in a rat hepatoma cell line was not significantly inhibited by preparations from either species. The data suggested that corresponding fractions from both rat and human liver could have inhibitory effects on precursor incorporation into DNA but the magnitude of the effects and target cell specificity may differ.

Reverse Transcriptase-Containing Particles Induced in Rous Sarcoma Virus-Transformed Rat Cells by Arginine Deprivation

Science.gov (United States)

Kotler, Moshe; Weinberg, Eynat; Haspel, Osnat; Becker, Yechiel

1972-01-01

Incubation of rat cells transformed by Rous sarcoma virus (RSV) in an arginine-deficient medium resulted in accumulation of particles in the culture medium. Such particles did not appear when the transformed rat cells were incubated in a complete medium nor in the medium of primary rat cells which were incubated either in arginine-deficient or complete media. The particles which were released from the arginine-deprived transformed rat cells resemble C-type particles in their properties. These particles band in sucrose gradients at a density of 1.16 g/ml and contain 35S ribonucleic acid (RNA) molecules and a reverse transcriptase activity. Analysis of the cytoplasm of transformed and primary rat cells, deprived and undeprived of arginine, revealed the presence of reverse transcriptase-containing particles which banded in sucrose gradients at a density of 1.14 g/ml. These particles differed from the particles released into the medium by the arginine-deprived RSV-transformed rat cells. The deoxyribonucleic acid (DNA) molecules synthesized in vitro by the reverse transcriptase present in the particles isolated from the medium of arginine-deprived cells hybridized to RSV RNA, whereas the DNA synthesized by the cell-bound enzyme had no homology to RSV RNA. PMID:4116137

[Red Blood Cells Raman Spectroscopy Comparison of Type Two Diabetes Patients and Rats].

Science.gov (United States)

Wang, Lei; Liu, Gui-dong; Mu, Xin; Xiao, Hong-bin; Qi, Chao; Zhang, Si-qi; Niu Wen-ying; Jiang, Guang-kun; Feng, Yue-nan; Bian, Jing-qi

2015-10-01

By using confocal Raman spectroscopy, Raman spectra were measured in normal rat red blood cells, normal human red blood cells, STZ induced diabetetic rats red blood cells, Alloxan induced diabetetic rats red blood cells and human type 2 diabetes red blood cells. Then principal component analysis (PCA) with support vector machine (SVM) classifier was used for data analysis, and then the distance between classes was used to judge the degree of close to two kinds of rat model with type 2 diabetes. The results found significant differences in the Raman spectra of red blood cell in diabetic and normal red blood cells. To diabetic red blood cells, the peak in the amide VI C=O deformation vibration band is obvious, and amide V N-H deformation vibration band spectral lines appear deviation. Belong to phospholipid fatty acyl C-C skeleton, the 1 130 cm(-1) spectral line is enhanced and the 1 088 cm(-1) spectral line is abated, which show diabetes red cell membrane permeability increased. Raman spectra of PCA combined with SVM can well separate 5 types of red blood cells. Classifier test results show that the classification accuracy is up to 100%. Through the class distance between the two induced method and human type 2 diabetes, it is found that STZ induced model is more close to human type 2 diabetes. In conclusion, Raman spectroscopy can be used for diagnosis of diabetes and rats STZ induced diabetes method is closer to human type 2 diabetes.

Expression of rat class I major histocompatibility complex (MHC) alloantigens and hepatocytes and hepatoma cells

International Nuclear Information System (INIS)

Hunt, J.M.; Desai, P.A.; Chakraborty, S.

1986-01-01

Altered expression of Class I MHC alloantigens has been reported for murine tumors, and may be associated with the tumorigenic phenotype of tumor cells. To characterize MHC Class I alloantigen expression on a chemically-induced transplantable rat hepatoma cell line, 17X, derived from a (WF x F344) F 1 rat, polyvalent anti-F344 and anti-WF rat alloantisera were first used to immunoprecipitate the rat RT1.A Class I MHC alloantigens expressed on primary (WF x F344) F 1 hepatocyptes in short-term monolayer cultures. Two-dimensional isoelectric focusing and SDS-PAGE of immunoprecipitates from 35 S-methionine-labeled (WF x F344) F 1 hepatocytes clearly resolved the RT1.A/sup u/ (WF) and RT1.A/sup LvI/ (F344) parental alloantigens. Identical radiolabeling and immunoprecipitation failed to detect either parental alloantigen on the 17X hepatoma cells. However, indirect immunofluorescence and immunoblot analyses demonstrated the presence of parental alloantigens on the 17X cells. Immunization of F344 rats but not of WF rats with 17X cells resulted in antibodies cytotoxic for normal (WF X F344) F 1 spleen cells in the presence of complement. These findings indicate that a combination of detection techniques will be necessary to characterize altered alloantigen expression on rat hepatoma cells

Pheochromocytoma complicated by intracerebral hemorrhage - a case report; Feocromocitoma complicado com acidente vascular encefalico hemorragico - relato de um caso

Energy Technology Data Exchange (ETDEWEB)

Nogueira, Aline Silva; Marchiori, Edson; Almeida, Fabiola Assuncao de; Martins, Renata Romano; Sales, Anderson Ribeiro; Santos, Tereza Cristina C.R.S. dos; Reis, Simone Teixeira [Universidade Federal Fluminense, Niteroi, RJ (Brazil). Dept. de Radiologia; Silveira, Sonia Marcelino T. da

1999-06-01

The authors report a case of pheochromocytoma that was complicated by intracerebral hemorrhage in a 17-year-old female patient. Computed tomography showed a solid mass, heterogeneous, on the right adrenal. The patient underwent a right adrenalectomy. She is being observed by our out-patients clinic, presenting normal blood pressure levels and a left hemiparesis. (author)

Preganglionic innervation of the pancreas islet cells in the rat

NARCIS (Netherlands)

LUITEN, PGM; TERHORST, GJ; KOOPMANS, SJ; RIETBERG, M; STEFFENS, AB

1984-01-01

The position and number of preganglionic somata innervating the insulin-secreting β-cells of the endocrine pancreas were investigated in Wistar rats. This question was approached by comparing the innervation of the pancreas of normal rats with the innervation of the pancreas in alloxan-induced

Establishment of bipotent progenitor cell clone from rat skeletal muscle.

Science.gov (United States)

Murakami, Yousuke; Yada, Erica; Nakano, Shin-ichi; Miyagoe-Suzuki, Yuko; Hosoyama, Tohru; Matsuwaki, Takashi; Yamanouchi, Keitaro; Nishihara, Masugi

2011-12-01

The present study describes the isolation, cloning and characterization of adipogenic progenitor cells from rat skeletal muscle. Among the obtained 10 clones, the most highly adipogenic progenitor, 2G11 cells, were further characterized. In addition to their adipogenicity, 2G11 cells retain myogenic potential as revealed by formation of multinucleated myotubes when co-cultured with myoblasts. 2G11 cells were resistant to an inhibitory effect of basic fibroblast growth factor on adipogenesis, while adipogenesis of widely used preadipogenic cell line, 3T3-L1 cells, was suppressed almost completely by the same treatment. In vivo transplantation experiments revealed that 2G11 cells are able to possess both adipogenicity and myogenicity in vivo. These results indicate the presence of bipotent progenitor cells in rat skeletal muscle, and suggest that such cells may contribute to ectopic fat formation in skeletal muscle. © 2011 The Authors. Animal Science Journal © 2011 Japanese Society of Animal Science.

EFFECTS OF VOLUNTARY WHEEL RUNNING ON SATELLITE CELLS IN THE RAT PLANTARIS MUSCLE

Directory of Open Access Journals (Sweden)

Atsushi Kojima

2009-03-01

Full Text Available This study investigated the effects of voluntary wheel running on satellite cells in the rat plantaris muscle. Seventeen 5-week-old male Wistar rats were assigned to a control (n = 5 or training (n = 12 group. Each rat in the training group ran voluntarily in a running-wheel cage for 8 weeks. After the training period, the animals were anesthetized, and the plantaris muscles were removed, weighed, and analyzed immunohistochemically and biochemically. Although there were no significant differences in muscle weight or fiber area between the groups, the numbers of satellite cells and myonuclei per muscle fiber, percentage of satellite cells, and citrate synthase activity were significantly higher in the training group compared with the control group (p < 0.05. The percentage of satellite cells was also positively correlated with distance run in the training group (r = 0.61, p < 0.05. Voluntary running can induce an increase in the number of satellite cells without changing the mean fiber area in the rat plantaris muscle; this increase in satellite cell content is a function of distance run

Stem Cell Therapy for Diabetic Erectile Dysfunction in Rats: A Meta-Analysis.

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Mingchao Li

Full Text Available Stem cell therapy is a novel method for the treatment of diabetic erectile dysfunction (ED. Many relative animal studies have been done to evaluate the efficacy of this therapy in rats.This meta-analysis was performed to compare the efficacy of different stem cell therapies, to evaluate the influential factors and to determine the optimal stem cell therapeutic strategy for diabetic ED.We searched the studies analyzing the efficacy of stem cell therapy for diabetic ED in rats published before September 30, 2015 in PubMed, Web of Science and EBSCO. A random effects meta-analysis was conducted to assess the outcomes of stem cell therapy. Subgroup analysis was also performed by separating these studies based on their different characteristics. Changes in the ratio of intracavernous pressure (ICP to mean arterial pressure (MAP and in the structure of the cavernous body were compared.10 studies with 302 rats were enrolled in this meta-analysis. Pooled analysis of these studies showed a beneficial effect of stem cell therapy in improving erectile function of diabetic rats (SMD 4.03, 95% CI = 3.22 to 4.84, P< 0.001. In the stem cell therapy group, both the smooth muscle and endothelium content were much more than those in control group. There was also significant increase in the expression of endothelial nitric oxide synthase (eNOS and neuronal nitric oxide synthase (nNOS, the ratio of smooth muscle to collagen, as well as the secretion of vascular endothelial growth factor (VEGF. Besides, apoptotic cells were reduced by stem cell treatment. The subgroup analysis indicated that modified stem cells were more effective than those without modification.Our results confirmed that stem cell therapy could apparently improve the erectile function of diabetic rats. Some specific modification, especially the gene modification with growth factors, could improve the efficacy of stem cell therapy. Stem cell therapy has potential to be an effective therapeutic

Lovastatin enhances in vitro radiation-induced apoptosis of rat B-cell lymphoma cells

International Nuclear Information System (INIS)

Rozados, V.R.; Hinrichsen, L.I.; Scharovsky, O.G.; Rosario Univ., Rosario; McDonnel, J.

2005-01-01

Our previous demonstration of an antimetastatic effect of lovastatin, both in rat sarcoma and lymphoma tumor-models, as well as the fact that lovastatin and radiation are able to stop the cell cycle in different phases, suggested the feasibility of a combined treatment. We studied the effect of the in vitro combined treatment of a B-cell rat lymphoma (L-TACB) with lovastatin and irradiation. The results herein obtained provide new information about the role of statins as radiosensitizers. The antitumor effect of the combined treatment was higher than that elicited by either treatment alone. This effect could be a consequence, at least in part, of an enhanced apoptosis

Ouabain binding to cultured vascular smooth muscle cells of the spontaneously hypertensive rat

International Nuclear Information System (INIS)

Hopp, L.; Khalil, F.; Tamura, H.; Kino, M.; Searle, B.M.; Tokushige, A.; Aviv, A.

1986-01-01

The binding of ouabain and K + to the Na + pump were analyzed in serially passed cultured vascular smooth muscle cells (VSMCs) originating from spontaneously hypertensive (SH) Wistar-Kyoto (WKY), and American Wistar (W) rats. The techniques have utilized analyses of displacement of [ 3 H]ouabain by both unlabeled ouabain and K + from specific binding sites on the VSMCs. The authors have found that 1) each of the VSMC preparations from the three rat strains appeared to demonstrate one population of specific ouabain receptors (Na + pumps); 2) the number of Na + pump units of both the SH and WKY rats was significantly lower than the number of Na + pump units of W rat VSMCs; 3) the equilibrium dissociation constant values (μM) for ouabain in VSMCs of SH and WKY rats were similar but were significantly higher than that of VSMCs derived from W rats; and 4) among the VSMCs originating from the three rat strains, the apparent equilibrium dissociation constant value for K + (mM) was the lowest in those of the SH rat compared with VSMCs of the WKY rat and W rat. Previous studies have demonstrated increased passive Na + and K + transport rate constants of SH rat VSMCs compared with either W or WKY rat cells. These findings suggest the possibility of higher permeabilities of the SH cells. They propose that the combined effect of a low number of Na + pump units with higher permeabilities to Na + and K + predisposes VSMCs of the SH rat to disturbances in their cellular ionic regulation. These genetic defects, if they occur in vivo, may lead to an increase in the vascular tone

The protective effect of fermented milk kefir on radiation-induced apoptosis in colonic crypt cells of rats

International Nuclear Information System (INIS)

Matsuu, Mutsumi; Shichijo, Kazuko; Okaichi, Kumio

2003-01-01

To evaluate the effect of fermented milk kefir on X-ray-induced apoptosis in the colon of rats, we examined the apoptotic index, the mean number of apoptotic cells detected by H and E staining per crypt in the colon, in control rats and kefir-pretreated rats drinking kefir for 12 days before irradiation. Apoptotic cells were confirmed by TUNEL staining, and active caspase-3 expression was studied by immunohistochemistry. The cell position of apoptotic cells and active caspase-3 positive cells were examined. The apoptotic index of kefir-treated rats was significantly (p<0.05) decreased 2 h after 1 Gy irradiation in comparison with control rats at crypt cell positions 1-3, 5-7, 13, and 15. Active caspase-3 expression in the kefir-treated rats was also significantly (p<0.05) reduced in comparison with control rats 2 h after 1 Gy irradiation at crypt cell positions 1-4, 13, and 15. This study indicated that kefir protects colonic crypt cells against radiation-induced apoptosis, which was most pronounced in the stem cell region of the crypt. The antiapoptotic effect of fermented milk kefir was due to the inhibition of caspase-3 activation. (author)

Testing stem cell therapy in a rat model of inflammatory bowel disease: role of bone marrow stem cells and stem cell factor in mucosal regeneration.

Science.gov (United States)

Qu, Bo; Xin, Guo-Rong; Zhao, Li-Xia; Xing, Hui; Lian, Li-Ying; Jiang, Hai-Yan; Tong, Jia-Zhao; Wang, Bei-Bei; Jin, Shi-Zhu

2014-01-01

The gastrointestinal (GI) mucosal cells turnover regularly under physiological conditions, which may be stimulated in various pathological situations including inflammation. Local epithelial stem cells appear to play a major role in such mucosal renewal or pathological regeneration. Less is clear about the involvement of multipotent stem cells from blood in GI repair. We attempted to explore a role of bone marrow mesenchymal stromal cells (BMMSCs) and soluble stem cell factor (SCF) in GI mucosa regeneration in a rat model of inflammatory bowel diseases (IBD). BMMSCs labelled with the fluorescent dye PKH26 from donor rats were transfused into rats suffering indomethacin-induced GI injury. Experimental effects by BMMSCs transplant and SCF were determined by morphometry of intestinal mucosa, double labeling of PKH26 positive BMMSCs with endogenous proliferative and intestinal cell markers, and western blot and PCR analyses of the above molecular markers in the recipient rats relative to controls. PKH26 positive BMMSCs were found in the recipient mucosa, partially colocalizing with the proliferating cell nuclear antigen (PCNA), Lgr5, Musashi-1 and ephrin-B3. mRNA and protein levels of PCNA, Lgr5, Musashi-1 and ephrin-B3 were elevated in the intestine in BMMSCs-treated rats, most prominent in the BMMSCs-SCF co-treatment group. The mucosal layer and the crypt layer of the small intestine were thicker in BMMSCs-treated rats, more evident in the BMMSCs-SCF co-treatment group. BMMSCs and SCF participate in but may play a synergistic role in mucosal cell regeneration following experimentally induced intestinal injury. Bone marrow stem cell therapy and SCF administration may be of therapeutic value in IBD.

Could Cells from Your Nose Fix Your Heart? Transplantation of Olfactory Stem Cells in a Rat Model of Cardiac Infarction

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Cameron McDonald

2010-01-01

Full Text Available This study examines the hypothesis that multipotent olfactory mucosal stem cells could provide a basis for the development of autologous cell transplant therapy for the treatment of heart attack. In humans, these cells are easily obtained by simple biopsy. Neural stem cells from the olfactory mucosa are multipotent, with the capacity to differentiate into developmental fates other than neurons and glia, with evidence of cardiomyocyte differentiation in vitro and after transplantation into the chick embryo. Olfactory stem cells were grown from rat olfactory mucosa. These cells are propagated as neurosphere cultures, similar to other neural stem cells. Olfactory neurospheres were grown in vitro, dissociated into single cell suspensions, and transplanted into the infarcted hearts of congeneic rats. Transplanted cells were genetically engineered to express green fluorescent protein (GFP in order to allow them to be identified after transplantation. Functional assessment was attempted using echocardiography in three groups of rats: control, unoperated; infarct only; infarcted and transplanted. Transplantation of neurosphere-derived cells from adult rat olfactory mucosa appeared to restore heart rate with other trends towards improvement in other measures of ventricular function indicated. Importantly, donor-derived cells engrafted in the transplanted cardiac ventricle and expressed cardiac contractile proteins.

Protective effects of peony glycosides against corticosterone-induced cell death in PC12 cells through antioxidant action.

Science.gov (United States)

Mao, Qing-Qiu; Xian, Yan-Fang; Ip, Siu-Po; Tsai, Sam-Hip; Che, Chun-Tao

2011-02-16

Previous studies in our laboratory have shown that total glycosides of peony (TGP) produced antidepressant-like action in various mouse models of behavioral despair. However, the molecular mechanism by which TGP exerts antidepressant-like effect is not fully understood. This study examined the protective effects of TGP against corticosterone-induced neurotoxicity in rat pheochromocytoma (PC12) cells and ts possible mechanisms. The direct antioxidant effect of TGP was investigated by using a 2,2'-azinobis-(3-ethylbenzothiazoline- 6-sulphonic acid) (ABTS) radical cation-scavenging assay in a cell-free system. PC12 cells were treated with 200 μM of corticosterone in the absence or presence of TGP in varying concentrations for 48 h. Cell viability, lactate dehydrogenase (LDH) activity, intracellular reactive oxygen species (ROS) level, malondialdehyde (MDA) content, glutathione (GSH) content, superoxide dismutase (SOD) activity, and catalase (CAT) activity were then determined. TGP displayed antioxidant properties in the cell-free system, and the IC50 value in the ABTS radical cation-scavenging assay was 9.9 mg/L. TGP treatment at increasing doses (1-10 mg/L) protected against corticosterone-induced cytotoxicity in PC12 cells in a dose-dependent manner. The cytoprotection afforded by TGP treatment was associated with decreases in the intracellular ROS and MDA levels, and increases in the GSH level, SOD activity, and CAT activity in corticosterone-treated PC12 cells. The results suggest that TGP has a neuroprotective effect on corticosterone-induced neurotoxicity in PC12 cells, which may be related to its antioxidant action. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Agnus castus extracts inhibit prolactin secretion of rat pituitary cells.

Science.gov (United States)

Sliutz, G; Speiser, P; Schultz, A M; Spona, J; Zeillinger, R

1993-05-01

In our studies on prolactin inhibition by plant extracts we focused on the effects of extracts of Vitex agnus castus and its preparations on rat pituitary cells under basal and stimulated conditions in primary cell culture. Both extracts from Vitex agnus castus as well as synthetic dopamine agonists (Lisuride) significantly inhibit basal as well as TRH-stimulated prolactin secretion of rat pituitary cells in vitro and as a consequence inhibition of prolactin secretion could be blocked by adding a dopamine receptor blocker. Therefore because of its dopaminergic effect Agnus castus could be considered as an efficient alternative phytotherapeutic drug in the treatment of slight hyperprolactinaemia.

Epithelial cell kinetics in mouse and rat skin irradiated with electrons

International Nuclear Information System (INIS)

McMaster-Schuyler, L.

1984-02-01

Experiments were performed to examine the kinetic responses of mouse and rat epidermal cells in vivo after single doses of ionizing radiation including responses of hair follicles at times after irradiation. The labeling indices in both species were reduced to 30 to 50% of control values immediately following irradiation at all the doses. In the rat, the labeling indices recovered and overshot control values within the first three days after 300 to 1200 rads. The mouse labeling indices continued to be suppressed for up to 10 days after 300 to 2400 rads. This indicated that rat G 1 phase epidermal cells recovered three times faster than those of the mouse with respect to the ability to maintain or increase control level cell proliferation after irradiation. After 1800 and 2400 rads, doses which produce skin ulceration, both species showed a reduction in their labeling indices for up to 7 days, indicating that a dose-dependent mechanism of recovery may be operable in the rat. 99 refs., 15 figs., 6 tabs

Effect of pirfenidone on the proliferation of rat corneal stromal cells

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Jun-Jie Chen

2015-02-01

Full Text Available AIM: To investigate the effects of pirfenidone(PFDon the proliferation and transfomring growth factor-β1(TGF-β1expression in vitro culture rat corneal stromal cells. METHODS: Corneal stromal cells from 8 to 10wk SD rats were isolated, cultured and treated with different concentrations of PFD 0mg/mL(control group, 0.15mg/mL(experimental group Ⅰ, 0.3mg/mL(experimental group Ⅱ, 1mg/mL(experimental group Ⅲfor 48h. CCK-8 assay was performed to assess cell proliferation, while immunocytochemistry and Western Blot were used to detect the expression of ki-67 and TGF-β1 expression, respectively. RESULTS: Compared with control group, PFD significantly inhibited the proliferation in a dose-dependent manner(all P1 in a dose-dependent manner(PCONCLUSION: Pirfenidone can significantly inhibit the proliferation of rat corneal stromal cell by down regulating TGF-β1 expression, therefore, it has potential prospect in lightening the corneal wound healing reaction.

Arginine vasopressin stimulates phosphoinositide turnover in an enriched rat Leydig cell preparation

DEFF Research Database (Denmark)

Nielsen, J.R.; Hansen, Harald S.; Jensen, B.

1989-01-01

An enriched rat Leydig cell preparation was preincubated with [C]arachidonic acid. Stimulation of the cells with arginine vasopressin (AVP) (1 µM) for 2 min caused a significant increase in labelled phosphatidic acid and a significant fall in radioactivity in phosphatidylinositol and phosphatidyl......An enriched rat Leydig cell preparation was preincubated with [C]arachidonic acid. Stimulation of the cells with arginine vasopressin (AVP) (1 µM) for 2 min caused a significant increase in labelled phosphatidic acid and a significant fall in radioactivity in phosphatidylinositol...

Establishment of 9L/F344 rat intracerebral glioma model of brain tumor stem cells

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Zong-yu XIAO

2015-04-01

Full Text Available Objective To establish the 9L/F344 rat intracerebral glioma model of brain tumor stem cells.  Methods Rat 9L gliosarcoma stem-like cells were cultured in serum-free suspension. The expression of CD133 and nestin were tested by immunohistochemistry. A total of 48 inbredline male F344 rats were randomly divided into 2 groups, and 9L tumor sphere cells and 9L monolayer cells were respectively implanted into the right caudate nucleus of F344 rats in 2 groups. Survival time was observed and determined using the method of Kaplan-Meier survival analysis. Fourteen days after implantation or when the rats were dying, their brains were perfused and sectioned for HE staining, and CD133 and nestin were detected by immunohistochemistry.  Results Rat 9L tumor spheres were formed with suspension culture in serum-free medium. The gliomas formed in both groups were invasive without obvious capsule. More new vessels, bleeding and necrosis could be detected in 9L tumor spheres group. The tumor cells in both groups were positive for CD133 and nestin. There was no significant difference in the expression of CD133 and nestin between 2 groups (P > 0.05, for all. According to the expression of nestin, the tumors formed by 9L tumor sphere cells were more invasive. The median survival time of the rats bearing 9L tumor sphere cells was 15 d (95%CI: 15.219-15.781, and the median survival time of the rats bearing 9L monolayer cells was 21 d (95%CI: 20.395-21.605. There was significant difference between 2 groups (χ2 = 12.800, P = 0.000.  Conclusions 9L/F344 rat intracerebral glioma model of brain tumor stem cells is successfully established, which provides a glioma model for the future research. DOI: 10.3969/j.issn.1672-6731.2015.04.012

GM-CSF-Producing Th Cells in Rats Sensitive and Resistant to Experimental Autoimmune Encephalomyelitis.

Science.gov (United States)

Stojić-Vukanić, Zorica; Pilipović, Ivan; Vujnović, Ivana; Nacka-Aleksić, Mirjana; Petrović, Raisa; Arsenović-Ranin, Nevena; Dimitrijević, Mirjana; Leposavić, Gordana

2016-01-01

Given that granulocyte macrophage colony-stimulating factor (GM-CSF) is identified as the key factor to endow auto-reactive Th cells with the potential to induce neuroinflammation in experimental autoimmune encephalomyelitis (EAE) models, the frequency and phenotype of GM-CSF-producing (GM-CSF+) Th cells in draining lymph nodes (dLNs) and spinal cord (SC) of Albino Oxford (AO) and Dark Agouti (DA) rats immunized for EAE were examined. The generation of neuroantigen-specific GM-CSF+ Th lymphocytes was impaired in dLNs of AO rats (relatively resistant to EAE induction) compared with their DA counterparts (susceptible to EAE) reflecting impaired CD4+ lymphocyte proliferation and less supportive of GM-CSF+ Th cell differentiation dLN cytokine microenvironment. Immunophenotyping of GM-CSF+ Th cells showed their phenotypic heterogeneity in both strains and revealed lower frequency of IL-17+IFN-γ+, IL-17+IFN-γ-, and IL-17-IFN-γ+ cells accompanied by higher frequency of IL-17-IFN-γ- cells among them in AO than in DA rats. Compared with DA, in AO rats was also found (i) slightly lower surface density of CCR2 (drives accumulation of highly pathogenic GM-CSF+IFN-γ+ Th17 cells in SC) on GM-CSF+IFN-γ+ Th17 lymphocytes from dLNs, and (ii) diminished CCL2 mRNA expression in SC tissue, suggesting their impaired migration into the SC. Moreover, dLN and SC cytokine environments in AO rats were shown to be less supportive of GM-CSF+IFN-γ+ Th17 cell differentiation (judging by lower expression of mRNAs for IL-1β, IL-6 and IL-23/p19). In accordance with the (i) lower frequency of GM-CSF+ Th cells in dLNs and SC of AO rats and their lower GM-CSF production, and (ii) impaired CCL2 expression in the SC tissue, the proportion of proinflammatory monocytes among peripheral blood cells and their progeny (CD45hi cells) among the SC CD11b+ cells were reduced in AO compared with DA rats. Collectively, the results indicate that the strain specificities in efficacy of several mechanisms

The SDH mutation database: an online resource for succinate dehydrogenase sequence variants involved in pheochromocytoma, paraganglioma and mitochondrial complex II deficiency

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Devilee Peter

2005-11-01

Full Text Available Abstract Background The SDHA, SDHB, SDHC and SDHD genes encode the subunits of succinate dehydrogenase (succinate: ubiquinone oxidoreductase, a component of both the Krebs cycle and the mitochondrial respiratory chain. SDHA, a flavoprotein and SDHB, an iron-sulfur protein together constitute the catalytic domain, while SDHC and SDHD encode membrane anchors that allow the complex to participate in the respiratory chain as complex II. Germline mutations of SDHD and SDHB are a major cause of the hereditary forms of the tumors paraganglioma and pheochromocytoma. The largest subunit, SDHA, is mutated in patients with Leigh syndrome and late-onset optic atrophy, but has not as yet been identified as a factor in hereditary cancer. Description The SDH mutation database is based on the recently described Leiden Open (source Variation Database (LOVD system. The variants currently described in the database were extracted from the published literature and in some cases annotated to conform to current mutation nomenclature. Researchers can also directly submit new sequence variants online. Since the identification of SDHD, SDHC, and SDHB as classic tumor suppressor genes in 2000 and 2001, studies from research groups around the world have identified a total of 120 variants. Here we introduce all reported paraganglioma and pheochromocytoma related sequence variations in these genes, in addition to all reported mutations of SDHA. The database is now accessible online. Conclusion The SDH mutation database offers a valuable tool and resource for clinicians involved in the treatment of patients with paraganglioma-pheochromocytoma, clinical geneticists needing an overview of current knowledge, and geneticists and other researchers needing a solid foundation for further exploration of both these tumor syndromes and SDHA-related phenotypes.

Ferritin expression in rat hepatocytes and Kupffer cells after lead nitrate treatment.

Science.gov (United States)

Fan, Yang; Yamada, Toshiyuki; Shimizu, Takeshi; Nanashima, Naoki; Akita, Miki; Suto, Kohji; Tsuchida, Shigeki

2009-02-01

Lead nitrate induces hepatocyte proliferation and subsequent apoptosis in rat livers. Iron is a constituent of heme and is also required for cell proliferation. In this study, the expression of ferritin light-chain (FTL), the major iron storage protein, was investigated in rat livers after a single intravenous injection of lead nitrate. Western blotting and immunohistochemistry revealed that FTL was increased in hepatocytes around the central veins and strongly expressed in nonparenchymal cells. Some FTL-positive nonparenchymal cells were identified as Kupffer cells that were positive for CD68. FTL-positive Kupffer cells occupied about 60% of CD68-positive cells in the periportal and perivenous areas. The relationships between FTL expression and apoptosis induction or the engulfment of apoptotic cells were examined. TUNEL-positive cells were increased in the treatment group, and enhanced expression of milk fat globule EGF-like 8 was demonstrated in some Kupffer cells and hepatocytes, indicating enhanced apoptosis induction and phagocytosis of apoptotic cells. FTL-positive Kupffer cells were not detected without lead nitrate treatment or in rat livers treated with clofibrate, which induces hepatocyte proliferation but not apoptosis. These results suggest that FTL expression in Kupffer cells after lead treatment is dependent on phagocytosis of apoptotic cells.

Ghrelin modulates testicular germ cells apoptosis and proliferation in adult normal rats

International Nuclear Information System (INIS)

Kheradmand, Arash; Dezfoulian, Omid; Alirezaei, Masoud; Rasoulian, Bahram

2012-01-01

Highlights: ► Spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. ► Numerous studies have documented the direct action of ghrelin in the modulation of apoptosis in different cell types. ► Ghrelin may be considered as a modulator of spermatogenesis in normal adult rats. ► Ghrelin may be potentially implicated for abnormal spermatogenesis in some testicular germ cell tumors. -- Abstract: Under normal condition in the most mammals, spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. The present study was designed to determine the effects of ghrelin treatment on in vivo quality and quantity expression of apoptosis and proliferation specific indices in rat testicular germ cells. Twenty eight adult normal rats were subdivided into equal control and treatment groups. Treatment group received 3 nmol of ghrelin as subcutaneous injection for 30 consecutive days or vehicle to the control animals. The rats from each group (n = 7) were killed on days 10 and 30 and their testes were taken for immunocytochemical evaluation and caspase-3 assay. Immunohistochemical analysis indicated that the accumulations of Bax and PCNA peptides are generally more prominent in spermatocytes and spermatogonia of both groups. Likewise, the mean percentage of immunoreactive spermatocytes against Bax increased (P 0.05). Upstream of Bax substance parallel to down-regulation of PCNA demonstrate that ghrelin may prevent massive accumulation of germ cells during normal spermatogenesis. These observations also indicate that ghrelin may be considered as a modulator of spermatogenesis in normal adult rats and could be potentially implicated for abnormal spermatogenesis in some testicular germ cell tumors.

Novel in vivo imaging techniques for trafficking the behavior of subventricular zone neural stem cells (SVZSC) and SVZSC induced functional repair

Energy Technology Data Exchange (ETDEWEB)

Anna-Liisa Brownell

2003-11-28

Adult progenitor cells hold promise for therapeutic treatment where there has been a disabling loss of function due to death of cells from trauma, disease or aging. However, it will be essential in clinical application to be able to follow the fate of the transplanted cells over time using in vivo tracking methods. We have developed protocol for labeling of progenitor cells to monitor cell trafficking by high resolution magnetic resonance imaging (MRI) and super high resolution positron emission tomography (PET). We have transfected rat subventricular zone stem cells (SVZ, progenitor cell line) and another control cell line (PC12, pheochromocytoma cells) utilizing super paramagnetic iron oxide and poly-L-lysine complex for MR imaging or radiolabeling with 18F-fluor deoxy-D- glucose for PET imaging. The labeled cells were transplanted into the rostral migratory stream (RMS) or striatum of normal or 6-hydroxydopamine lesioned Spraque-Dawley rats. Longitudinal MRI studies (up to 40 days) showed that transplantation site has significant impact to the fate of the cells; when SVZ cells were transplanted into the RMS, cells migrated several centimeter into the olfactory bulb; after transplantation into the striatum, the migration was minimal, only 2 mm. PC 12 cells grew a massive tumor after the striatal implantation and significantly smaller tumor after the RMS implantation. PET studies conducted immediately after transplantation verified the transplantation site. MRI studies were able to show the whole path of migration in one image, since part of the cells die during migration and will get detected because of iron content. Endpoint histological studies verified the cell survival and immunohistochemical studies revealed the differentiation of the transplanted cells into astrocytes and neurons.

Novel in vivo imaging techniques for trafficking the behavior of subventricular zone neural stem cells (SVZSC) and SVZSC induced functional repair

International Nuclear Information System (INIS)

Anna-Liisa Brownell

2003-01-01

Adult progenitor cells hold promise for therapeutic treatment where there has been a disabling loss of function due to death of cells from trauma, disease or aging. However, it will be essential in clinical application to be able to follow the fate of the transplanted cells over time using in vivo tracking methods. We have developed protocol for labeling of progenitor cells to monitor cell trafficking by high resolution magnetic resonance imaging (MRI) and super high resolution positron emission tomography (PET). We have transfected rat subventricular zone stem cells (SVZ, progenitor cell line) and another control cell line (PC12, pheochromocytoma cells) utilizing super paramagnetic iron oxide and poly-L-lysine complex for MR imaging or radiolabeling with 18F-fluor deoxy-D- glucose for PET imaging. The labeled cells were transplanted into the rostral migratory stream (RMS) or striatum of normal or 6-hydroxydopamine lesioned Spraque-Dawley rats. Longitudinal MRI studies (up to 40 days) showed that transplantation site has significant impact to the fate of the cells; when SVZ cells were transplanted into the RMS, cells migrated several centimeter into the olfactory bulb; after transplantation into the striatum, the migration was minimal, only 2 mm. PC 12 cells grew a massive tumor after the striatal implantation and significantly smaller tumor after the RMS implantation. PET studies conducted immediately after transplantation verified the transplantation site. MRI studies were able to show the whole path of migration in one image, since part of the cells die during migration and will get detected because of iron content. Endpoint histological studies verified the cell survival and immunohistochemical studies revealed the differentiation of the transplanted cells into astrocytes and neurons

Efficacy of Mesenchymal Stem Cells in Suppression of Hepatocarcinorigenesis in Rats: Possible Role of Wnt Signaling

LENUS (Irish Health Repository)

Abdel Aziz, Mohamed T

2011-05-05

Abstract Background The present study was conducted to evaluate the tumor suppressive effects of bone marrow derived mesenchymal stem cells (MSCs) in an experimental hepatocellular carcinoma (HCC) model in rats and to investigate the possible role of Wnt signaling in hepato-carcinogenesis. Methods Ninety rats were included in the study and were divided equally into: Control group, rats which received MSCs only, rats which received MSCs vehicle only, HCC group induced by diethylnitroseamine (DENA) and CCl 4 , rats which received MSCs after HCC induction, rats which received MSCs before HCC induction. Histopathological examination and gene expression of Wnt signaling target genes by real time, reverse transcription-polymerase chain reaction (RT-PCR) in rat liver tissue, in addition to serum levels of ALT, AST and alpha fetoprotein were performed in all groups. Results Histopathological examination of liver tissue from animals which received DENA-CCl4 only, revealed the presence of anaplastic carcinoma cells and macro-regenerative nodules type II with foci of large and small cell dysplasia. Administration of MSCs into rats after induction of experimental HCC improved the histopathological picture which showed minimal liver cell damage, reversible changes, areas of cell drop out filled with stem cells. Gene expression in rat liver tissue demonstrated that MSCs downregulated β-catenin, proliferating cell nuclear antigen (PCNA), cyclin D and survivin genes expression in liver tissues after HCC induction. Amelioration of the liver status after administration of MSCs has been inferred by the significant decrease of ALT, AST and Alpha fetoprotein serum levels. Administration of MSCs before HCC induction did not show any tumor suppressive or protective effect. Conclusions Administration of MSCs in chemically induced HCC has tumor suppressive effects as evidenced by down regulation of Wnt signaling target genes concerned with antiapoptosis, mitogenesis, cell proliferation

Committed T lymphocyte stem cells of rats. Characterization by surface W3/13 antigen and radiosensitivity

International Nuclear Information System (INIS)

Dyer, M.J.; Hunt, S.V.

1981-01-01

The existence of stem cells committed to the T lymphoid lineage was deduced from studying how rat T and B stem cells differ in their expression of membrane W3/13 antigen and in their susceptibility in vivo to gamma irradiation. Stem cell activity of rat bone marrow and fetal liver was measured in long-term radiation chimeras using B and T cell alloantigenic surface markers to identify the progeny of donor cells. Monoclonal mouse anti-rat thymocyte antibody W3/13 labeled approximately 40% of fetal liver cells and 60-70% of young rat bone marrow cells (40% brightly, 25% dimly). Bright, dim, and negative cells were separated on a fluorescence-activated cell sorter. All B and T lymphoid stem cells in fetal liver were W3/13 bright, as were B lymphoid stem cells in bone marrow. W3/13 dim bone marrow had over half the T cell repopulating activity of unseparated marrow but gave virtually no B cell repopulation. In further experiments, the radiosensitivity of endogenous B and T lymphoid stem cells was determined by exposing host rats to between 4.5 and 10 Gy of gamma irradiation before repopulation with genetically marked marrow. The results depended on whether chimerism was assayed before day 50 or after day 100. At early times, a radioresistant T stem cell was indicated, whose activity waned later. Thus committed T stem cells of rats carry moderate amounts of W3/13 antigen and are more radioresistant but less permanently chimeragenic than the stem cells that regenerate B lymphocytes

Communication between mast cells and rat submucosal neurons.

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Bell, Anna; Althaus, Mike; Diener, Martin

2015-08-01

Histamine is a mast cell mediator released e.g. during food allergy. The aim of the project was to identify the effect of histamine on rat submucosal neurons and the mechanisms involved. Cultured submucosal neurons from rat colon express H1, H2 and H3 receptors as shown by immunocytochemical staining confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) with messenger RNA (mRNA) isolated from submucosal homogenates as starting material. Histamine evoked a biphasic rise of the cytosolic Ca(2+) concentration in cultured submucosal neurons, consisting in a release of intracellularly stored Ca(2+) followed by an influx from the extracellular space. Although agonists of all three receptor subtypes evoked an increase in the cytosolic Ca(2+) concentration, experiments with antagonists revealed that mainly H1 (and to a lesser degree H2) receptors mediate the response to histamine. In coculture experiments with RBL-2H3 cells, a mast cell equivalent, compound 48/80, evoked an increase in the cytosolic Ca(2+) concentration of neighbouring neurons. Like the response to native histamine, the neuronal response to the mast cell degranulator was strongly inhibited by the H1 receptor antagonist pyrilamine and reduced by the H2 receptor antagonist cimetidine. In rats sensitized against ovalbumin, exposure to the antigen induced a rise in short-circuit current (I sc) across colonic mucosa-submucosa preparations without a significant increase in paracellular fluorescein fluxes. Pyrilamine strongly inhibited the increase in I sc, a weaker inhibition was observed after blockade of protease receptors or 5-lipoxygenase. Consequently, H1 receptors on submucosal neurons seem to play a pivotal role in the communication between mast cells and the enteric nervous system.

Establishment of rat embryonic stem-like cells from the morula using a combination of feeder layers.

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Sano, Chiaki; Matsumoto, Asako; Sato, Eimei; Fukui, Emiko; Yoshizawa, Midori; Matsumoto, Hiromichi

2009-08-01

Embryonic stem (ES) cells are characterized by pluripotency, in particular the ability to form a germline on injection into blastocysts. Despite numerous attempts, ES cell lines derived from rat embryos have not yet been established. The reason for this is unclear, although certain intrinsic biological differences among species and/or strains have been reported. Herein, using Wistar-Imamichi rats, specific characteristics of preimplantation embryos are described. At the blastocyst stage, Oct4 (also called Pou5f1) was expressed in both the inner cell mass (ICM) and the trophectoderm (TE), whereas expression of Cdx2 was localized to the TE. In contrast, at an earlier stage, expression of Oct4 was detected in all the nuclei in the morula. These stages were examined using a combination of feeder layers (rat embryonic fibroblast [REF] for primary outgrowth and SIM mouse embryo-derived thioguanine- and ouabain-resistant [STO] cells for passaging) to establish rat ES-like cell lines. The rat ES-like cell lines obtained from the morula maintained expression of Oct4 over long-term culture, whereas cell lines derived from blastocysts lost pluripotency during early passage. The morula-derived ES-like cell lines showed Oct4 expression in a long-term culture, even after cryogenic preservation, thawing and EGFP transfection. These results indicate that rat ES-like cell lines with long-term Oct4 expression can be established from the morula of Wistar-Imamichi rats using a combination of feeder layers.

Pheochromocytoma (PC12 Cell Response on Mechanobactericidal Titanium Surfaces

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Jason V. Wandiyanto

2018-04-01

Full Text Available Titanium is a biocompatible material that is frequently used for making implantable medical devices. Nanoengineering of the surface is the common method for increasing material biocompatibility, and while the nanostructured materials are well-known to represent attractive substrata for eukaryotic cells, very little information has been documented about the interaction between mammalian cells and bactericidal nanostructured surfaces. In this study, we investigated the effect of bactericidal titanium nanostructures on PC12 cell attachment and differentiation—a cell line which has become a widely used in vitro model to study neuronal differentiation. The effects of the nanostructures on the cells were then compared to effects observed when the cells were placed in contact with non-structured titanium. It was found that bactericidal nanostructured surfaces enhanced the attachment of neuron-like cells. In addition, the PC12 cells were able to differentiate on nanostructured surfaces, while the cells on non-structured surfaces were not able to do so. These promising results demonstrate the potential application of bactericidal nanostructured surfaces in biomedical applications such as cochlear and neuronal implants.

Antioxidation activities of pteridines in mammalian cell lines

Energy Technology Data Exchange (ETDEWEB)

Zhang, Y.; Shen, R. (Univ. of Texas, Galveston (United States))

1991-03-11

L-erythro-5,6,7,8-Tetrahydrobiopterin (BH{sub 4}), the cofactor for aromatic amino acid hydroxylases (AAA-H), is a predominant form of pteridines which occur ubiquitously in nature. When BH{sub 4} is oxidized to quinonoid dihydrobiopterin by AAA-H, it is regenerated by dihydropteridine reductase (DHPR) at the expense of NADH. The role of BH{sub 4} other than serving as the hydroxylase cofactor is not clear. The existence of BH{sub 4} and DHPR in tissues which are devoid of AAA-H suggests that BH{sub 4} may play an as yet undiscovered physiological function. This study demonstrates a BH{sub 4}-mediated antioxidation system, which consists of BH{sub 4}, DHPR, peroxidase and NADH in rat pheochromocytoma PC 12 cells and mouse macrophages J774A.1. This system was as effective as catalase and ascorbic acid in protecting cells against H{sub 2}O{sub 2} and xanthine/xanthine oxidase-induced toxicity and was more effective than catalase in defense against nitrofurantoin-induced toxicity. The antioxidation effect of this system was not due to peroxidase and was improved when synthetic pteridines were substituted for BH{sub 4}. Since BH{sub 4}, DHPR, peroxidases and NADH are widely distributed in major organs and blood cells, they may constitute an as yet little known antioxidation system in mammalian cells.

Rats, cats, and elephants, but still no unicorn: induced pluripotent stem cells from new species.

Science.gov (United States)

Trounson, Alan

2009-01-09

Two independent studies in this issue of Cell Stem Cell (Liao et al., 2009; Li et al., 2009) derive rat induced pluripotent stem cells (iPSCs). In one report, the method used results in rat and human iPSCs that exhibit phenotypic traits similar to mouse embryonic stem cells.

Cell proliferation and apoptosis in rat mammary glands following combinational exposure to bisphenol A and genistein

International Nuclear Information System (INIS)

Wang, Jun; Jenkins, Sarah; Lamartiniere, Coral A

2014-01-01

Humans are exposed to an array of both harmful and beneficial hormonally active compounds in the environment and through diet. Two such chemicals are Bisphenol A (BPA), a plasticizer, and genistein, a component of soy. Prepubertal exposure to BPA increased mammary carcinogenesis, while genistein suppressed cancer in a chemically-induced model of rodent mammary cancer. The purpose of this research was to determine the effects of combinational exposure to genistein and BPA on cell proliferation, apoptosis, and associated proteins as markers of cancer in mammary glands of rats exposed prepubertally to these environmental chemicals. Prepubertal rats (postpartum days (PND) 2–20) were exposed through lactation via nursing dams treated orally with sesame oil (SO), BPA, genistein, or a combination of BPA and genistein (BPA + Gen). Cell proliferation, apoptosis and protein expressions were investigated for mechanistic studies in mammary glands of rats exposed to these environmental chemicals. Prepubertal exposure to genistein increased cell proliferation in mammary glands of PND21 rats, while BPA increased cell proliferation in adult (PND50) rats. Prepubertal combinational exposure to BPA + Gen increased cell proliferation and reduced apoptosis in PND21 rats, but reduced cell proliferation and increased apoptosis in PND50 rats. The altered mechanisms behind these cellular responses appear to be centered on differential protein expression of caspases, PARP, Bad, p21, Akts, PTEN, ER-β and SRCs 1–3, in the rat mammary gland. Prepubertal BPA exposure resulted in increased cell proliferation in mammary glands of PND50 rats, a process associated with increased risk of cancer development in a chemically-induced mammary cancer. On the other hand, genistein stimulated cell proliferation at PND21, a process that correlates with mammary gland maturation and chemoprevention. In contrast to single chemical exposure, combinational exposure to BPA + Gen performed most similarly to

Effect of continuous low-dose γ-irradiation on rat Sertoli cell function

International Nuclear Information System (INIS)

Kamtchouing, P.; Papadopoulos, V.; Drosdowsky, M.A.; Carreau, S.; Pinon-Lataillade, G.; Maas, J.; Guillaumin, J.M.; Bardos, P.; Perreau, C.; Hochereau de Reviers, M.T.

1988-01-01

Continuous low-dose γ-irradiation of mature rats induced a progressive degeneration of the germ cells. Blood FSH increased by 127, 176 and 214%, respectively, after 55, 70 and 85 days of treatment when compared to FSH levels in control rats (8.50 ± 0.60 ng/ml); conversely, serum LH and testosterone levels were unchanged. The Sertoli cell function was affected by the treatment from 70 days on, as attested by androgen binding protein (ABP) and transferrin secretions which diminished 35-40%. Serum ABP levels were not altered, whatever the duration of irradiation, even though epididymal ABP contents (as well as concentrations) diminished 34-60% when compared to those of the controls. Moreover, in purified Leydig cells, LH-stimulated intracellular cAMP levels, which were decreased by seminiferous tubule medium (STM) from control rats, were enhanced in presence of STM from treated animals. Testosterone output was stimulated 9-fold in presence of oLH and further increased (46-76%) from stages XIV-V by STM prepared from control and irradiated rats, respectively. After 85 days the STM effects on both cAMP and testosterone syntheses were zero. These results demonstrate a probable alteration of Sertoli cell function after irradiation, but also a role of the germ cells in the regulation of the synthesis of ABP, transferrin and Sertoli cell paracrine factors

Canine tracheal epithelial cells are more sensitive than rat tracheal epithelial cells to transforming growth factor beta induced growth inhibition

International Nuclear Information System (INIS)

Hubbs, A.F.; Hahn, F.F.; Kelly, G.; Thomassen, D.G.

1988-01-01

Transforming growth factor beta (TGFβ) markedly inhibited growth of canine tracheal epithelial (CTE) cells. Reduced responsiveness to TGFβ-induced growth inhibition accompanied neoplastic progression of these cells from primary to transformed to neoplastic. This was similar to the relationship between neoplastic progression and increased resistance to TGFβ-induced growth inhibition seen for rat tracheal epithelial (RTE) cells. The canine cells were more sensitive than rat cells to TGFβ-induced growth inhibition at all stages in the neoplastic process. (author)

Neuroprotective and behavioral efficacy of intravenous transplanted adipose stem cells in experimental Parkinsonian rat models

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Malihe Nakhaeifard

2016-02-01

Full Text Available Background: Parkinson's disease is a deficiency of dopamine in the striatum, characterized by bradykinesis, rigidity and resting tremor. Adipose tissue-Derived Stem Cells (ADSCs have many advantages for cell therapy because of the easy availability and pluripotency without ethical problems. In this research, the effects of ADSCs transplantation on motor impairment of rat Parkinsonian models were evaluated. Materials and Methods: Parkinson model was constructed by the unilateral lesion of striatum of male Wistar rats using 20µg of 6-hydroxydopamine (6-OHDA as lesion group. Cell and α-MEM (α-minimal essential medium groups were lesioned animals that received intravenous injection of 3×106 cells suspended in medium and medium repectively. All rats were evaluated behaviorally with rotarod and apomorphine-induced rotation tests, at 4 and 8 weeks after cell transplantation. Results: Lesion and α-MEM groups showed increased contralateral turns while cell group significantly ameliorated both in rotarod and apomorphine-induced rotation tests. There was a significant difference of contralateral turns between cell and lesioned groups at 8 weeks after transplantation. Lesioned rats showed significant decrease of staying on the rod as compared to control, but in cell group there was a significant increase in comparision with the lesioned animals. Conclusion: ADSCs injected intravenously promote functional recovery in Parkinsonian rats.

Urtica Dioica Distillate Regenerates Pancreatic Beta Cells in Streptozotocin-Induced Diabetic Rats

Science.gov (United States)

Gohari, Ali; Noorafshan, Ali; Akmali, Masoumeh; Zamani-Garmsiri, Fahimeh; Seghatoleslam, Atefeh

2018-01-01

Background Urtica dioica is known as an anti-hyperglycemic plant. Urtica dioica distillate (UD) is a traditional Iranian drink, locally known as “aragh gazaneh”. In spite of its widespread consumption in Iran, according to traditional Iranian medicine, there is no scientific report on the usefulness of UD for diabetic patients. This survey was designed to evaluate its protective effects for the recovery from diabetes by determining the serum insulin, blood glucose, volume of pancreatic islets, and the number and volume of β-cells in diabetic rats. Methods A total of 48 Sprague-Dawley male rats (200-250 g) were randomly distributed into 6 groups (n=8), including non-diabetic plus distilled water (DW), non-diabetic plus UD, diabetic plus DW, diabetic plus UD, diabetic plus insulin, and diabetic plus glibenclamide. DW, UD, and glibenclamide were administered via intragastric gavage and insulin was injected subcutaneously. After four weeks of experiments, blood samples were collected for serum insulin and blood glucose assay. Pancreas was also evaluated using stereological method. The SPSS software was used for statistical analysis. Kruskal-Wallis, repeated measurements, and Mann-Whitney U test were applied for comparisons between the groups. Results The treatment of diabetic rats with UD reduced the blood glucose dramatically (P<0.001) and increased serum insulin levels significantly (P=0.03) in comparison to the diabetic plus DW rats. Treatment with UD did not affect the mean β-cell volumes in the diabetic rats when compared to the diabetic plus DW rats, but the islet volumes and β-cell numbers were significantly recovered. Conclusion UD treatment in diabetic rats improves hyperglycemia by partially restoring plasma insulin levels. The data suggest that UD prevents islet atrophy and/or regenerate pancreatic β-cells. PMID:29749986

Comparison of therapeutic characteristics of islet cell transplantation simultaneous with pancreatic mesenchymal stem cell transplantation in rats with Type 1 diabetes mellitus.

Science.gov (United States)

Unsal, Ilknur Ozturk; Ginis, Zeynep; Pinarli, Ferda Alparslan; Albayrak, Aynur; Cakal, Erman; Sahin, Mustafa; Delibasi, Tuncay

2015-06-01

Although, pancreas islet call transplantation is a new, promising method for type 1 diabetic patients, it remains as an experimental procedure applied in selected patients. The present study aimed to investigate effect of pancreatic mesenchymal stem cell transplantation simultaneous with islet cell transplantation on islet liveliness and thus on the treatment of diabetes in type 1 diabetic rats. The study used Wistar Albino Rats and was performed in a total of four groups [control (G1), mesenchymal stem cell (G2), islet (G3) and islet + mesencymal stem cell (G4)] each including 8 rats. Blood glucose level of the rats, in which diabetes model has been created using streptozotocin, was measured after 72 h. Blood samples were obtained from the rats 30 days after transplantation and then, their livers and pancreases were kept in 10% formaldehyde and the experiment was ended. Following staining with H&E, they were morphologically evaluated under a light microscope. Change in mean blood glucose level was statistically significant in G3 and G4 versus G1 and G2 (p = 0.001, p islet cells in the pancreases of the rats was higher in G4; difference between the groups was statistically significant (p Transplantation of islet cells together with mesenchymal stem cells showed beneficial effects in terms of prolonging survival of islet grafts suggesting that transplantation of mesenchymal stem cells together with islet cells during clinical islet transplantation may be beneficial in increasing the number of noninsulin-dependent patients in Type 1 diabetes.

Feocromocitoma: uma causa rara de hipertensão arterial na infância Pheochromocytoma: a rare cause of hypertension in childhood

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Flávia Carolina D. Georgetti

2007-09-01

Full Text Available OBJETIVO: Relatar o caso de um adolescente com feocromocitoma, uma causa rara de hipertensão arterial na infância. DESCRIÇÃO: Adolescente internado em unidade de terapia intensiva infantil em decorrência de emergência hipertensiva, conseqüente à presença de feocromocitoma em adrenal esquerda, diagnosticado por meio de tomografia computadorizada do abdome e pela dosagem de adrenalina e noradrenalina urinárias. O paciente foi submetido à adrenalectomia esquerda, após o uso de alfa-bloqueador para controle do quadro hipertensivo. O anatomopatológico confirmou o diagnóstico do tumor. No pós-operatório, o paciente permaneceu estável, possibilitando a suspensão dos anti-hipertensivos. COMENTÁRIOS: Os feocromocitomas são tumores capazes de produzir catecolaminas, especialmente adrenalina e/ou noradrenalina. Cerca de 85 a 95% dos tumores são únicos, benignos e encontrados na medula adrenal. O feocromocitoma é um tumor de incidência rara e apenas 10 a 20% ocorrem na infância, representando uma causa rara de hipertensão arterial. Esta última é um sinal freqüente na maioria das crianças (80%, podendo ser acompanhada por cefaléia e sudorese. A encefalopatia hipertensiva consiste em uma forma de apresentação excepcional da doença. O diagnóstico pode ser realizado, na maioria dos casos, pela tomografia de abdome e pela dosagem das catecolaminas e seus metabólitos produzidos pelo tumor. O tratamento de escolha consiste na ressecção completa do tumor após o preparo farmacológico do paciente com o uso de alfa-bloqueador. No pós-operatório, a maioria dos pacientes evolui com controle do quadro de hipertensão arterial.OBJECTIVE: Report an adolescent with pheochromocytoma, a rare cause of hypertension in childhood. CASE DESCRIPTION: Adolescent admitted to the pediatric intensive care unit due to hypertension, secondary to the presence of pheochromocytoma on the left adrenal. Diagnosis of the pheochromocytoma was made by

Human embryonic stem cell-derived cells rescue visual function in dystrophic RCS rats.

Science.gov (United States)

Lund, Raymond D; Wang, Shaomei; Klimanskaya, Irina; Holmes, Toby; Ramos-Kelsey, Rebeca; Lu, Bin; Girman, Sergej; Bischoff, N; Sauvé, Yves; Lanza, Robert

2006-01-01

Embryonic stem cells promise to provide a well-characterized and reproducible source of replacement tissue for human clinical studies. An early potential application of this technology is the use of retinal pigment epithelium (RPE) for the treatment of retinal degenerative diseases such as macular degeneration. Here we show the reproducible generation of RPE (67 passageable cultures established from 18 different hES cell lines); batches of RPE derived from NIH-approved hES cells (H9) were tested and shown capable of extensive photoreceptor rescue in an animal model of retinal disease, the Royal College of Surgeons (RCS) rat, in which photoreceptor loss is caused by a defect in the adjacent retinal pigment epithelium. Improvement in visual performance was 100% over untreated controls (spatial acuity was approximately 70% that of normal nondystrophic rats) without evidence of untoward pathology. The use of somatic cell nuclear transfer (SCNT) and/or the creation of banks of reduced complexity human leucocyte antigen (HLA) hES-RPE lines could minimize or eliminate the need for immunosuppressive drugs and/or immunomodulatory protocols.

Effect of Light and Darkness on Packed Cell Volume in the Rat ...

African Journals Online (AJOL)

The aim of the study is to identify and characterize the circadian oscillation of Packed Cell Volume (PCV) within a 24-hour time frame in adult Sprague-Dawley rats. 56 adult Sprague-Dawley rats consists of 28 male and 28 female rats were used. Male animals weighed 150-170g while the females weighed 130140g.

Quantitative analysis of rat Ig (sub)classes binding to cell surface antigens

International Nuclear Information System (INIS)

Nilsson, R.; Brodin, T.; Sjoegren, H.-O.

1982-01-01

An indirect 125 I-labeled protein A assay for detection of cell surface-bound rat immunoglobulins is presented. The assay is quantitative and rapid and detects as little as 1 ng of cell surface-bound Ig. It discriminates between antibodies belonging to different IgG subclasses, IgM and IgA. The authors describe the production and specificity control of the reagents used and show that the test can be used for quantitative analysis. A large number of sera from untreated rats are tested to evaluate the frequency of falsely positive responses and variation due to age, sex and strain of rat. With this test it is relatively easy to quantitate the binding of classes and subclasses of rat immunoglobulins in a small volume (6 μl) of untreated serum. (Auth.)

Ureter smooth muscle cell orientation in rat is predominantly longitudinal.

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Bart Spronck

Full Text Available In ureter peristalsis, the orientation of the contracting smooth muscle cells is essential, yet current descriptions of orientation and composition of the smooth muscle layer in human as well as in rat ureter are inconsistent. The present study aims to improve quantification of smooth muscle orientation in rat ureters as a basis for mechanistic understanding of peristalsis. A crucial step in our approach is to use two-photon laser scanning microscopy and image analysis providing objective, quantitative data on smooth muscle cell orientation in intact ureters, avoiding the usual sectioning artifacts. In 36 rat ureter segments, originating from a proximal, middle or distal site and from a left or right ureter, we found close to the adventitia a well-defined longitudinal smooth muscle orientation. Towards the lamina propria, the orientation gradually became slightly more disperse, yet the main orientation remained longitudinal. We conclude that smooth muscle cell orientation in rat ureter is predominantly longitudinal, though the orientation gradually becomes more disperse towards the proprial side. These findings do not support identification of separate layers. The observed longitudinal orientation suggests that smooth muscle contraction would rather cause local shortening of the ureter, than cause luminal constriction. However, the net-like connective tissue of the ureter wall may translate local longitudinal shortening into co-local luminal constriction, facilitating peristalsis. Our quantitative, minimally invasive approach is a crucial step towards more mechanistic insight into ureter peristalsis, and may also be used to study smooth muscle cell orientation in other tube-like structures like gut and blood vessels.

Ureter smooth muscle cell orientation in rat is predominantly longitudinal.

Science.gov (United States)

Spronck, Bart; Merken, Jort J; Reesink, Koen D; Kroon, Wilco; Delhaas, Tammo

2014-01-01

In ureter peristalsis, the orientation of the contracting smooth muscle cells is essential, yet current descriptions of orientation and composition of the smooth muscle layer in human as well as in rat ureter are inconsistent. The present study aims to improve quantification of smooth muscle orientation in rat ureters as a basis for mechanistic understanding of peristalsis. A crucial step in our approach is to use two-photon laser scanning microscopy and image analysis providing objective, quantitative data on smooth muscle cell orientation in intact ureters, avoiding the usual sectioning artifacts. In 36 rat ureter segments, originating from a proximal, middle or distal site and from a left or right ureter, we found close to the adventitia a well-defined longitudinal smooth muscle orientation. Towards the lamina propria, the orientation gradually became slightly more disperse, yet the main orientation remained longitudinal. We conclude that smooth muscle cell orientation in rat ureter is predominantly longitudinal, though the orientation gradually becomes more disperse towards the proprial side. These findings do not support identification of separate layers. The observed longitudinal orientation suggests that smooth muscle contraction would rather cause local shortening of the ureter, than cause luminal constriction. However, the net-like connective tissue of the ureter wall may translate local longitudinal shortening into co-local luminal constriction, facilitating peristalsis. Our quantitative, minimally invasive approach is a crucial step towards more mechanistic insight into ureter peristalsis, and may also be used to study smooth muscle cell orientation in other tube-like structures like gut and blood vessels.

Major salivary gland hypertrophy model in immature rats: morphometric and histochemical epithelial cell characteristics

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Vera V. Ivanova

2017-01-01

Full Text Available The purpose of the study is to estimate the functional state of epithelial cells of acini and ducts of major salivary glands with hypertrophy caused by repeated incisor amputations in immature rats.Materials and methods. The experiment was carried out on immature (20 days, white male rats, divided into 3 groups: intact, control and group of rats with repeated incisor amputations. Animals were taken out in 2d, 3d, 4th, 6th, 8th, 10th and 12th weeks after the first incisor amputation. Morphofunctional state of rat major salivary glands was assessed by histological (hematoxylin and eosin, histochemistrical (Alcian blue, PAS-reaction, Brachet method and morphometrical (acini area, intralobular ducts volume methods.Results. Repeated incisor amputations led to the increase of acini area and the decrease of intralobular duct volume in submandibular glands in 2nd–4th weeks of the experiment. Cytoplasm pyroninophilia of submandibular gland acinar cells was less pronounced and intensity of PAS-reaction was more pronounced than in intact animals in 3rd week of the experiment. Morphological and functional changes of parotid and sublingual gland epithelial cells were not observed after repeated amputations of incisors in immature rats.Conclusion. Repeated incisor amputations in immature male rats lead to submandibular gland acinar cell hypertrophy in the early stages of the experiment (2d–4th weeks with accumulation of glycoproteins and protein synthesis weakening in these cells. Hypertrophy of acinar cells are accompanied by retardation in the development of granular convoluted tubule cells which are the source of synthesis and secretion of the endocrine biologically active factors of submandibular glands.

Sustained glucagon-like peptide 1 expression from encapsulated transduced cells to treat obese diabetic rats.

Science.gov (United States)

Moralejo, Daniel; Yanay, Ofer; Kernan, Kelly; Bailey, Adam; Lernmark, Ake; Osborne, William

2011-04-01

Obesity and type 2 diabetes (T2D) are two prevalent chronic diseases that have become a major public health concern in industrialized countries. T2D is characterized by hyperglycemia and islet beta cell dysfunction. Glucagon-like peptide 1 (GLP-1) promotes β cell proliferation and neogenesis and has a potent insulinotropic effect. Leptin receptor deficient male rats are obese and diabetic and provide a model of T2D. We hypothesized that their treatment by sustained expression of GLP-1 using encapsulated cells may prevent or delay diabetes onset. Vascular smooth muscle cells (VSMC) retrovirally transduced to secrete GLP-1 were seeded into TheraCyte(TM) encapsulation devices, implanted subcutaneously and rats were monitored for diabetes. Rats that received cell implants showed mean plasma GLP-1 level of 119.3 ± 10.2pM that was significantly elevated over control values of 32.4 ± 2.9pM (P<0.001). GLP-1 treated rats had mean insulin levels of 45.9 ± 2.3ng/ml that were significantly increased over control levels of 7.3±1.5ng/ml (P<0.001). In rats treated before diabetes onset elevations in blood glucose were delayed and rats treated after onset became normoglycemic and showed improved glucose tolerance tests. Untreated diabetic rats possess abnormal islet structures characterized by enlarged islets with α-cell infiltration and multifocal vacuolization. GLP-1 treatment induced normalization of islet structures including a mantle of α-cells and increased islet mass. These data suggest that encapsulated transduced cells may offer a potential long term treatment of patients. Copyright © 2010 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Effect of TheraCyte-encapsulated parathyroid cells on lumbar fusion in a rat model.

Science.gov (United States)

Chen, Sung-Hsiung; Huang, Shun-Chen; Lui, Chun-Chung; Lin, Tzu-Ping; Chou, Fong-Fu; Ko, Jih-Yang

2012-09-01

Implantation of TheraCyte 4 × 10(6) live parathyroid cells can increase the bone marrow density of the spine of ovariectomized rats. There has been no published study examining the effect of such implantation on spinal fusion outcomes. The purpose of this study was to examine the effect of TheraCyte-encapsulated parathyroid cells on posterolateral lumbar fusions in a rat model. Forty Sprague-Dawley rats underwent single-level, intertransverse process spinal fusions using iliac crest autograft. The rats were randomly assigned to two groups: Group 1 rats received sham operations on their necks (control; N = 20); Group 2 rats were implanted with TheraCyte-encapsulated 4 × 10(6) live parathyroid cells into the subcutis of their necks (TheraCyte; N = 20). Six weeks after surgery the rats were killed. Fusion was assessed by inspection, manual palpation, radiography, and histology. Blood was drawn to measure the serum levels of calcium, phosphorus, and intact parathyroid hormone (iPTH). Based on manual palpation, the control group had a fusion rate of 33 % (6/18) and the TheraCyte group had a fusion rate of 72 % (13/18) (P = 0.044). Histology confirmed the manual palpation results. Serum iPTH levels were significantly higher in the TheraCyte group compared with the control group (P TheraCyte-encapsulated 4 × 10(6) live parathyroid cells than in control rats without significant change in serum calcium or phosphorus concentrations. As with any animal study, the results may not extrapolate to a higher species. Further studies are needed to determine if these effects are clinically significant.

Protective Action of Carica papaya on β-Cells in Streptozotocin-Induced Diabetic Rats

Science.gov (United States)

Miranda-Osorio, Pedro H.; Castell-Rodríguez, Andrés E.; Vargas-Mancilla, Juan; Tovilla-Zárate, Carlos A.; Ble-Castillo, Jorge L.; Aguilar-Domínguez, Dora E.; Juárez-Rojop, Isela E.; Díaz-Zagoya, Juan C.

2016-01-01

The aim of the present study was to investigate the effect of C. papaya L. leaf extract (CPLE) on pancreatic islets in streptozotocin (STZ)-induced diabetic rats, as well as on cultured normal pancreatic cells with STZ in the medium. CPLE (3–125 mg/Kg) was administered orally for 20 days, while a group of diabetic rats received 5 IU/Kg/day of insulin. At the end of the treatment the rats were sacrificed. Blood was obtained to assess glucose and insulin levels. The pancreas was dissected to evaluate β cells by immunohistochemistry. In addition, normal pancreatic cells were cultured in a medium that included CPLE (3–12 mg). One half of the cultured cells received simultaneously CPLE and STZ (6 mg), while the other half received CPLE and five days later the STZ. After three days of incubation, insulin was assayed in the incubation medium. The CPLE administered to diabetic rats improved the fasting glycemia and preserved the number and structure of pancreatic islets. However, when CPLE was added to pancreatic cells in culture along with STZ, the insulin concentration was higher in comparison with the cells that only received STZ. In conclusion, the CPLE preserves the integrity of pancreatic islets, improves the basal insulin secretion and protects cultured cells from the adverse effects of STZ. PMID:27128930

The influence of sexual hormones on lipogenesis and lipolysis in rat fat cells

DEFF Research Database (Denmark)

Hansen, Finn Mølgård; Fahmy, N; Nielsen, Jens Høiriis

1980-01-01

and prooestrus than in dioestrus. Oestradiol treatment of both female and male rats and testosterone treatment of male rats for three days lowered the fatty acid synthesis and increased the lipolysis. The metabolic oscillation disappeared in ovariectomized rats, and the fat cells from these animals showed...

Ghrelin modulates testicular germ cells apoptosis and proliferation in adult normal rats

Energy Technology Data Exchange (ETDEWEB)

Kheradmand, Arash, E-mail: arashkheradmand@yahoo.com [Department of Clinical Sciences, School of Veterinary Medicine, Lorestan University, P.O. Box: 465, Khorram Abad (Iran, Islamic Republic of); Dezfoulian, Omid [Department of Pathobiology, School of Veterinary Medicine, Lorestan University, Khorram Abad (Iran, Islamic Republic of); Alirezaei, Masoud [Division of Biochemistry, School of Veterinary Medicine, Lorestan University, P.O. Box: 465, Khorram Abad (Iran, Islamic Republic of); Rasoulian, Bahram [Razi Herbal Medicine Research Center, Lorestan University of Medical Sciences, Khorram Abad (Iran, Islamic Republic of)

2012-03-09

Highlights: Black-Right-Pointing-Pointer Spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. Black-Right-Pointing-Pointer Numerous studies have documented the direct action of ghrelin in the modulation of apoptosis in different cell types. Black-Right-Pointing-Pointer Ghrelin may be considered as a modulator of spermatogenesis in normal adult rats. Black-Right-Pointing-Pointer Ghrelin may be potentially implicated for abnormal spermatogenesis in some testicular germ cell tumors. -- Abstract: Under normal condition in the most mammals, spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. The present study was designed to determine the effects of ghrelin treatment on in vivo quality and quantity expression of apoptosis and proliferation specific indices in rat testicular germ cells. Twenty eight adult normal rats were subdivided into equal control and treatment groups. Treatment group received 3 nmol of ghrelin as subcutaneous injection for 30 consecutive days or vehicle to the control animals. The rats from each group (n = 7) were killed on days 10 and 30 and their testes were taken for immunocytochemical evaluation and caspase-3 assay. Immunohistochemical analysis indicated that the accumulations of Bax and PCNA peptides are generally more prominent in spermatocytes and spermatogonia of both groups. Likewise, the mean percentage of immunoreactive spermatocytes against Bax increased (P < 0.01) in the ghrelin-treated group on day 10, while despite of 30% increment in the Bax level of spermatocytes in the treated rats on day 30, however, it was not statistically significant. During the experimental period, only a few spermatogonia represented Bax expression and the changes of Bax immunolabling cells were negligible upon ghrelin treatment. Likewise, there were immunostaining cells against Bcl-2 in each germ cell neither in the control nor in the treated animals. In fact

Isolation and characterization of dental epithelial cells derived from amelogenesis imperfecta rat.

Science.gov (United States)

Adiningrat, A; Tanimura, A; Miyoshi, K; Hagita, H; Yanuaryska, R D; Arinawati, D Y; Horiguchi, T; Noma, T

2016-03-01

Disruption of the third zinc finger domain of specificity protein 6 (SP6) presents an enamel-specific defect in a rat model of amelogenesis imperfecta (AMI rats). To understand the molecular basis of amelogenesis imperfecta caused by the Sp6 mutation, we established and characterized AMI-derived rat dental epithelial (ARE) cells. ARE cell clones were isolated from the mandibular incisors of AMI rats, and amelogenesis-related gene expression was analyzed by reverse transcription polymerase chain reaction (RT-PCR). Localization of wild-type SP6 (SP6WT) and mutant-type SP6 (SP6AMI) was analyzed by immunocytochemistry. SP6 transcriptional activity was monitored by rho-associated protein kinase 1 (Rock1) promoter activity with its specific binding to the promoter region in dental (G5 and ARE) and non-dental (COS-7) epithelial cells. Isolated ARE cells were varied in morphology and gene expression. Both SP6WT and SP6AMI were mainly detected in nuclei. The promoter analysis revealed that SP6WT and SP6AMI enhanced Rock1 promoter activity in G5 cells but that enhancement by SP6AMI was weaker, whereas no enhancement was observed in the ARE and COS-7 cells, even though SP6WT and SP6AMI bound to the promoter in all instances. ARE cell clones can provide a useful in vitro model to study the mechanism of SP6-mediated amelogenesis imperfecta. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Antioxidant activity and phenylpropanoids of Phlomis lychnitis L

DEFF Research Database (Denmark)

López, Víctor; Jäger, Anna Katharina; Akerreta, Silvia

2010-01-01

Phlomis lychnitis L. (Lamiaceae) is consumed as a traditional herbal tea in Spain. The antioxidant-protective effects as well as its phytoconstituents have never been established. The ability of the methanolic extract to protect cells from oxidative stress was evaluated in rat pheochromocytoma...... of the plant to scavenge ABTS, DPPH, O(2) . (-) radicals and to inhibit XO. Bioassay guided fractionation led to antioxidant compounds. Qualitative HPLC/DAD/ESI/MS analysis reported phenylpropanoids, verbascoside being the major antioxidant constituent....

The Therapeutic Effect of Human Embryonic Stem Cell-Derived Multipotent Mesenchymal Stem Cells on Chemical-Induced Cystitis in Rats

Directory of Open Access Journals (Sweden)

Sang Wook Lee

2018-01-01

Full Text Available Purpose To evaluate the therapeutic effect of human embryonic stem cell (hESC-derived multipotent mesenchymal stem cells (M-MSCs on ketamine-induced cystitis (KC in rats. Methods To induce KC, 10-week-old female rats were injected with 25-mg/kg ketamine hydrochloride twice weekly for 12 weeks. In the sham group, phosphate buffered saline (PBS was injected instead of ketamine. One week after the final injection of ketamine, the indicated doses (0.25, 0.5, and 1×106 cells of M-MSCs (KC+M-MSC group or PBS vehicle (KC group were directly injected into the bladder wall. One week after M-MSC injection, the therapeutic outcomes were evaluated via cystometry, histological analyses, and measurement of gene expression. Next, we compared the efficacy of M-MSCs at a low dose (1×105 cells to that of an identical dose of adult bone marrow (BM-derived MSCs. Results Rats in the KC group exhibited increased voiding frequency and reduced bladder capacity compared to rats of the sham group. However, these parameters recovered after transplantation of M-MSCs at all doses tested. KC bladders exhibited markedly increased mast cell infiltration, apoptosis, and tissue fibrosis. Administration of M-MSCs significantly reversed these characteristic histological alterations. Gene expression analyses indicated that several genes associated with tissue fibrosis were markedly upregulated in KC bladders. However the expression of these genes was significantly suppressed by the administration of M-MSCs. Importantly, M-MSCs ameliorated bladder deterioration in KC rats after injection of a low dose (1×105 of cells, at which point BM-derived MSCs did not substantially improve bladder function. Conclusions This study demonstrates for the first time the therapeutic efficacy of hESC-derived M-MSCs on KC in rats. M-MSCs restored bladder function more effectively than did BM-derived MSCs, protecting against abnormal changes including mast cell infiltration, apoptosis and fibrotic

Postnatal treadmill exercise alleviates short-term memory impairment by enhancing cell proliferation and suppressing apoptosis in the hippocampus of rat pups born to diabetic rats.

Science.gov (United States)

Kim, Young Hoon; Sung, Yun-Hee; Lee, Hee-Hyuk; Ko, Il-Gyu; Kim, Sung-Eun; Shin, Mal-Soon; Kim, Bo-Kyun

2014-08-01

During pregnancy, diabetes mellitus exerts detrimental effects on the development of the fetus, especially the central nervous system. In the current study, we evaluated the effects of postnatal treadmill exercise on short-term memory in relation with cell proliferation and apoptosis in the hippocampus of rat pups born to streptozotocin (STZ)-induced diabetic maternal rats. Adult female rats were mated with male rats for 24 h. Two weeks after mating, the pregnant female rats were divided into two groups: control group and STZ injection group. The pregnant rats in the STZ injection group were administered 40 mg/kg of STZ intraperitoneally. After birth, the rat pups were divided into the following four groups: control group, control with postnatal exercise group, maternal STZ-injection group, and maternal STZ-injection with postnatal exercise group. The rat pups in the postnatal exercise groups were made to run on a treadmill for 30 min once a day, 5 times per week for 2 weeks beginning 4 weeks after birth. The rat pups born to diabetic rats were shown to have short-term memory impairment with suppressed cell proliferation and increased apoptosis in the hippocampal dentate gyrus. Postnatal treadmill exercise alleviated short-term memory impairment by increased cell proliferation and suppressed apoptosis in the rat pups born to diabetic rats. These findings indicate that postnatal treadmill exercise may be used as a valuable strategy to ameliorate neurodevelopmental problems in children born to diabetics.

Repair effect of transplantation of bone marrow mesenchymal stem cells on liver injury in severe burned rats and its mechanism

International Nuclear Information System (INIS)

Chen Hao; Zhou Yubo; Zhang Ying; Qin Yonggang; Guo Li; Yin Fei; Meng Chunyang; Yang Xiaoyu

2014-01-01

Objective: To investigate the repair effect of transplantation of bone marrow mesenchymal stem cells (BMSCs) on liver injury in severe burned rats, and to clarify its mechanism. Methods: The BMSCs of rats were isolated, cultured, amplified, identified, and labeled in vitro. 30 Wistar rats were randomly divided into normal control group (n=10), model group (n=10) and cell therapy group (n=10). The burned rat model was established. The BMSCs labeled by chlormethyl-benzamidodialkylcarbocyanine (CM-Dil) were transplanted into the rats in cell therapy group by retro-orbital intravenous injection and the saline was injected into the rats in model group. The general status of all rats were observed. The liver tissues of rats were obtained 2 weeks after transplantation, and the pathohistological changes were observed and the pathohistological scores were detected; the apoptotic rate of liver cells was detected by TUNEL method; the engraftment of BMSCs in liver tissues of the rats was observed under laser scanning confocal microscope. Results: 2 weeks after transplantation, the rats in model group were obviously malaise dispirited and the rats in cell therapy group showed obviously better, and the body weight of the rats in cell therapy group was higher than that in model group (P<0.05). The pathohistological results showed the normal liver lobules of the rats in model group disappeared, and the liver cords disordered, and some liver sinusoids dilated and congested, lymphocytes infiltrated with occasional focal aggregating, and cell edema was found, cytoplasm loose and steatosis were seen in liver tissue. However, the pathohistological changes of liver tissue of the rats in cell therapy group were significantly better than those in model group. The pathohistological score of the rats in cell therapy group was significantly lower than that in model group (P<0.05). The TUNEL staining results showed that there were lots of apoptotic liver cells in liver tissue of the rats in

Scintigraphic localization of a disseminated malignant pheochromocytoma with the use of 131I-meta-iodobenzylguanidine

International Nuclear Information System (INIS)

Troncone, L.; Maini, L.M.; Rufini, V.; Bonifazi, N.; De Rosa, G.; Corsello, S.M.; Mattei, O.

1984-01-01

Preliminary clinical studies with 131 I-meta-iodo-benzylguanidine, a newly synthesized radiopharmaceutical and guanethidine analog capable of imaging the adrenal medulla, have led to the identification, of a case of disseminated malignant pheochromocytoma with the localization of brain and bone metastases. The result is of particular interest as the symptomatology in this case appeared rather equivocal and various investigations had led to a completely different diagnosis. This new scintigraphic technique has proved to be safe, specific and noninvasive, and it may have a clinical application as a complementary or alternative technique to conventional diagnostic tests. (orig.)

Effect of TheraCyte-encapsulated parathyroid cells on lumbar fusion in a rat model

OpenAIRE

Chen, Sung-Hsiung; Huang, Shun-Chen; Lui, Chun-Chung; Lin, Tzu-Ping; Chou, Fong-Fu; Ko, Jih-Yang

2012-01-01

Introduction Implantation of TheraCyte 4 × 106 live parathyroid cells can increase the bone marrow density of the spine of ovariectomized rats. There has been no published study examining the effect of such implantation on spinal fusion outcomes. The purpose of this study was to examine the effect of TheraCyte-encapsulated parathyroid cells on posterolateral lumbar fusions in a rat model. Materials and methods Forty Sprague-Dawley rats underwent single-level, intertransverse process spinal fu...

Splenectomy enhances the therapeutic effect of adipose tissue-derived mesenchymal stem cell infusion on cirrhosis rats.

Science.gov (United States)

Tang, Wei-Ping; Akahoshi, Tomohiko; Piao, Jing-Shu; Narahara, Sayoko; Murata, Masaharu; Kawano, Takahito; Hamano, Nobuhito; Ikeda, Tetsuo; Hashizume, Makoto

2016-08-01

Clinical studies suggest that splenectomy improves liver function in cirrhotic patients, but the influence of splenectomy on stem cell transplantation is poorly understood. This study investigated the effect of splenectomy on stem cell infusion and elucidated its mechanism. Rat adipose tissue-derived mesenchymal stem cells were infused into cirrhosis rats with or without splenectomy, followed by the assessment of the in vivo distribution of stem cells and pathological changes. Stromal cell-derived factor-1 and hepatocyte growth factor expression were also investigated in splenectomized cirrhosis patients and rats. Splenectomy, prior to cell infusion, improved liver function and suppressed fibrosis progression more efficiently than cell infusion alone in the experimental cirrhosis model. Stromal cell-derived factor-1 and hepatocyte growth factor levels after splenectomy were increased in patients and rats. These upregulated cytokines significantly facilitated stem cell motility, migration and proliferation in vitro. C-X-C chemokine receptor type 4 neutralization weakened the promotion of cell migration by these cytokines. The infused cells integrated into liver fibrosis septa and participated in regeneration more efficiently in splenectomized rats. Direct coculture with stem cells led to inhibition of hepatic stellate cell proliferation. In addition, hepatocyte growth factor induced hepatic stellate cell apoptosis via the c-jun N-terminal kinase-p53 pathway. Splenectomy prior to cell infusion enhanced the therapeutic effect of stem cells on cirrhosis, which involved upregulation of stromal cell-derived factor-1 and hepatocyte growth factor after splenectomy. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effect of benazepril on the transdifferentiation of renal tubular epithelial cells from diabetic rats.

Science.gov (United States)

Peng, Tao; Wang, Jie; Zhen, Junhui; Hu, Zhao; Yang, Xiangdong

2014-07-01

The aim of this study was to investigate the effect of benazepril on the transdifferentiation of renal tubular epithelial cells from diabetic rats. Thirty male Sprague-Dawley rats were included in the present study. Eight of the 30 rats were randomly selected and served as the normal control group (N group), while the remaining 22 rats, injected with streptozotocin (STZ), comprised the diabetic rat model. Rats with diabetes were randomly divided into the diabetic (DM group) and benazepril (B group) groups. The total course was conducted over 12 weeks. Blood glucose, body weight, kidney/body weight, 24-h urinary protein, serum creatinine and blood urea nitrogen were measured at the start and end of the study. We observed the tubulointerstitial pathological changes, and applied immunohistochemistry and western blotting to detect the expression of α-smooth muscle actin (α-SMA) in renal tissue. The levels of blood glucose, kidney/body weight, 24-h urinary protein, serum creatinine, blood urea nitrogen and tubulointerstitial damage index (TII) in the DM group were significantly higher than that in the N group (pbenazepril significantly reduced the expression of α-SMA in renal tubular epithelial cells obtained from diabetic rats, inhibited the transdifferentiation of renal tubular epithelial cells and played an important role in kidney protection.

Usefulness of standardized uptake values for distinguishing adrenal glands with pheochromocytoma from normal adrenal glands by use of 6-18F-fluorodopamine PET.

NARCIS (Netherlands)

Timmers, H.J.L.M.; Carrasquillo, J.A.; Whatley, M.A.; Eisenhofer, G.; Chen, C.C.; Ling, A.; Linehan, W.M.; Pinto, P.A.; Adams, K.T.; Pacak, K.

2007-01-01

6-(18)F-Fluorodopamine ((18)F-FDA) PET is a highly sensitive tool for the localization of pheochromocytoma (PHEO). The aim of this study was to establish cutoff values for pathologic and physiologic adrenal gland tracer uptake. METHODS: (18)F-FDA PET with CT coregistration was performed in 14

Protective effect of arctigenin on ethanol-induced neurotoxicity in PC12 cells.

Science.gov (United States)

Huang, Jia; Xiao, Lan; Wei, Jing-Xiang; Shu, Ya-Hai; Fang, Shi-Qi; Wang, Yong-Tang; Lu, Xiu-Min

2017-04-01

As a neurotropic substance, ethanol can damage nerve cells through an increase in the production of free radicals, interference of neurotrophic factor signaling pathways, activation of endogenous apoptotic signals and other molecular mechanisms. Previous studies have revealed that a number of natural drugs extracted from plants offer protection of nerve cells from damage. Among these, arctigenin (ATG) is a lignine extracted from Arctium lappa (L.), which has been found to exert a neuroprotective effect on scopolamine‑induced memory deficits in mice with Alzheimer's disease and glutamate-induced neurotoxicity in primary neurons. As a result, it may offer beneficial effects on ethanol-induced neurotoxicity. However, the effects of ATG on ethanol‑induced nerve damage remain to be elucidated. To address this issue, the present study used rat pheochromocytoma PC12 cells to investigate the neuroprotective effects of ATG on ethanol-induced cell damage by performing an MTT reduction assay, cell cycle analysis, Hoechst33342/propidium iodide fluorescence staining and flow cytometry to examine apoptosis. The results showed that 10 µM ATG effectively promoted the proliferation of damaged cells, and increased the distribution ratio of the cells at the G2/M and S phases (P<0.05). In addition, the apoptosis and necrosis of the PC12 cells were significantly decreased following treatment with ATG. Therefore, it was concluded that 10 µM ATG had a protective effect on ethanol‑induced injury in PC12 cells.

Cellular location of rat muscle ferritins and their preferential loss during cell isolation.

Science.gov (United States)

Linder, M C; Roboz, M; McKown, M J; Pardridge, W M; Zak, R

1984-04-10

Heart and other muscles of the rat contain two forms of ferritin separable in polyacrylamide gel electrophoresis. The cellular location of the fast- and slow-migrating ferritins was investigated using primary cultures of hindlimb skeletal muscle, and isolated myocardial cell populations. Muscle and non-muscle cells were isolated in good yield from hearts of adult rats pretreated with large doses of iron to increase their ferritin content. In virtually all cases, the isolated muscle cells contained traces only of the fast-migrating species and the non-muscle cells contained small amounts of the slow-migrating ferritin. During cell isolation, 90-100% of both ferritins was lost and could be recovered in the perfusates and solutions employed, while one third of the total tissue protein, and a larger percentage of creatine phosphokinase, was recovered in the isolated cells. Primary cultures of thigh muscle from adult rats which had differentiated into multi-nucleated myotubes, were incubated for 1-3 days with chelated iron. These cells contained substantial amounts of the electrophoretically fast migrating ferritin, with its characteristic larger Stokes' radius (determined by quantitative polyacrylamide gel electrophoresis). None of the slow-migrating ferritin species was detected, although hindlimb muscle from iron-treated rats contained both forms. It is concluded that the fast-migrating ferritin of muscle, which is much larger and more asymmetric than other ferritins, is confined to the muscle cell population, while the other form is predominantly or exclusively in the non-muscle cells. Both ferritins are lost preferentially over other proteins during procedures which injure muscle tissue.

Effect of Gsk3 inhibitor CHIR99021 on aneuploidy levels in rat embryonic stem cells.

Science.gov (United States)

Bock, Anagha S; Leigh, Nathan D; Bryda, Elizabeth C

2014-06-01

Germline competent embryonic stem (ES) cells can serve as a tool to create genetically engineered rat strains used to elucidate gene function or provide disease models. In optimum culture conditions, ES cells are able to retain their pluripotent state. The type of components present and their concentration in ES cell culture media greatly influences characteristics of ES cells including the ability to maintain the cells in a pluripotent state. We routinely use 2i media containing inhibitors CHIR99021 and PD0325901 to culture rat ES cells. CHIR99021 specifically inhibits the Gsk3β pathway. We have found that the vendor source of CHIR99021 has a measurable influence on the level of aneuploidy seen over time as rat ES cells are passaged. Karyotyping of three different rat ES cell lines passaged multiple times showed increased aneuploidy when CHIR99021 from source B was used. Mass spectrometry analysis of this inhibitor showed the presence of unexpected synthetic small molecules, which might directly or indirectly cause increases in chromosome instability. Identifying these molecules could further understanding of their influence on chromosome stability and indicate how to improve synthesis of this media component to prevent deleterious effects in culture.

Impaired succinic dehydrogenase activity of rat Purkinje cell mitochondria during aging.

Science.gov (United States)

Fattoretti, P; Bertoni-Freddari, C; Caselli, U; Paoloni, R; Meier-Ruge, W

1998-03-16

The perikaryal Purkinje cell mitochondria positive to the copper ferrocyanide histochemical reaction for succinic dehydrogenase (SDH) have been investigated by means of semiautomatic morphometric methods in rats of 3, 12 and 24 months of age. The number of organelles/microm3 of Purkinje cell cytoplasm (Numeric density: Nv), the average mitochondrial volume (V) and the mitochondrial volume fraction (Volume density: Vv) were the ultrastructural parameters taken into account. Nv was significantly higher at 12 than at 3 and 24 months of age. V was significantly decreased at 12 and 24 months of age, but no difference was envisaged between adult and old rats. Vv was significantly decreased in old animals vs. the other age groups. In young and old rats, the percentage of organelles larger than 0.32 microm3 was 13.5 and 11%, respectively, while these enlarged mitochondria accounted for less than 1% in the adult group. Since SDH activity is of critical importance when energy demand is high, the marked decrease of Vv supports an impaired capacity of the old Purkinje cells to match actual energy supply at sustained transmission of the nervous impulse. However, the high percentage of enlarged organelles found in old rats may witness a morphofunctional compensatory response.

Black seed oil ameliorates allergic airway inflammation by inhibiting T-cell proliferation in rats.

Science.gov (United States)

Shahzad, Muhammad; Yang, Xudong; Raza Asim, M B; Sun, Qingzhu; Han, Yan; Zhang, Fujun; Cao, Yongxiao; Lu, Shemin

2009-02-01

The black seeds, from the Ranunculaceae family, have been traditionally used by various cultures as a natural remedy for several ailments. In this study, we examined the effect of black seed oil as an immunomodulator in a rat model of allergic airway inflammation. Rats sensitized to ovalbumin and challenged intranasally with ovalbumin to induce an allergic inflammatory response were compared to ovalbumin-sensitized, intranasally ovalbumin-exposed rats pretreated with intraperitoneally administered black seed oil and to control rats. The levels of IgE, IgG1 and ova-specific T-cell proliferation in spleen were measured by ELISA. The pro-inflammatory cytokine IL-4, IL-5, IL-6 and TGF-beta1 mRNA expression levels were measured by reverse transcription polymerase chain reaction. The intraperitoneal administration of black seed oil inhibited the Th2 type immune response in rats by preventing inflammatory cell infiltration and pathological lesions in the lungs. It significantly decreased the nitric oxide production in BALF, total serum IgE, IgG1 and OVA-specific IgG1 along with IL-4, IL-5, IL-6 and TGF-beta1 mRNA expression. Black seed oil treatment resulted in decreased T-cell response evident by lesser delayed type hypersensitivity and lower T-cell proliferation in spleen. In conclusion, black seed oil exhibited a significant reduction in all the markers of allergic inflammation mainly by inhibiting the delayed type hypersensitivity and T-cell proliferation. The data suggests that inhibition of T-cell response may be responsible for immunomodulatory effect of black seed oil in the rat model of allergic airway inflammation.

Rat hepatic β2-adrenergic receptor: structural similarities to the rat fat cell β1-adrenergic receptor

International Nuclear Information System (INIS)

Graziano, M.P.

1984-01-01

The mammalian β 2 -adrenergic receptor from rat liver has been purified by sequential cycles of affinity chromatography followed by steric-exclusion high performance liquid chromatography. Electrophoresis of highly purified receptor preparations on polyacrylamide gels in the presence of sodium dodecyl sulfate under reducing conditions reveals a single peptide M/sub r/ = 67,000, as judged by silver staining. Purified β 2 -adrenergic receptor migrates on steric-exclusion high performance liquid chromatography in two peaks, with M/sub r/ = 140,000 and 67,000. Specific binding of the high affinity, β-adrenergic receptor antagonists (-)[ 3 H]dihydroalprenolol and (-)[ 125 I]iodocyanopindolol to purified rat liver β-adrenergic receptor preparations displays stereoselectivity for (-)isomers of agonists and a rank order of potencies for agonists characteristics of a β 2 -adrenergic receptor. Radioiodinated, β 1 -adrenergic receptors from rat fat cells and β 2 -adrenergic receptors from rat liver purified in the presence of protease inhibitors comigrate in electrophoretic separations on polyacrylamide gels in the presence of sodium dodecyl sulfate as 67,000-M/sub r/ peptides. Autoradiograms of two dimensional partial proteolytic digests of the purified, radioiodinated rat liver β 2 -adrenergic receptor, generated with α-chymotrypsin, S. aureus V8 protease and elastase reveal a pattern of peptide fragments essentially identical to those generated by partial proteolytic digests of the purified, radioiodinated β 1 -adrenergic receptor from rat fat cells, by these same proteases. These data indicate that a high degree of homology exists between these two pharmacologically distinct mammalian β-adrenergic receptor proteins

Catecholamine secretion by chemical hypoxia in guinea-pig, but not rat, adrenal medullary cells: differences in mitochondria.

Science.gov (United States)

Harada, K; Endo, Y; Warashina, A; Inoue, M

2015-08-20

The effects of mitochondrial inhibitors (CN(-), a complex IV inhibitor and CCCP, protonophore) on catecholamine (CA) secretion and mitochondrial function were explored functionally and biochemically in rat and guinea-pig adrenal chromaffin cells. Guinea-pig chromaffin cells conspicuously secreted CA in response to CN(-) or CCCP, but rat cells showed a little, if any, secretory response to either of them. The resting metabolic rates in rat adrenal medullae did not differ from those in guinea-pig adrenal medullae. On the other hand, the time course of depolarization of the mitochondrial membrane potential (ΔΨm) in guinea-pig chromaffin cells in response to CN(-) was slower than that in rat chromaffin cells, and this difference was abolished by oligomycin, an F1F0-ATPase inhibitor. The extent of CCCP-induced decrease in cellular ATP in guinea-pig chromaffin cells, which was indirectly measured using a Mg(2+) indicator, was smaller than that in rat chromaffin cells. Relative expression levels of F1F0-ATPase inhibitor factor in guinea-pig adrenal medullae were smaller than in rat adrenal medullae, and the opposite was true for F1F0-ATPase α subunit. The present results indicate that guinea-pig chromaffin cells secrete more CA in response to a mitochondrial inhibitor than rat chromaffin cells and this higher susceptibility in the former is accounted for by a larger extent of reversed operation of F1F0-ATPase with the consequent decrease in ATP under conditions where ΔΨm is depolarized. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Cell Injury and Repair Resulting from Sleep Loss and Sleep Recovery in Laboratory Rats

Science.gov (United States)

Everson, Carol A.; Henchen, Christopher J.; Szabo, Aniko; Hogg, Neil

2014-01-01

Study Objectives: Increased cell injury would provide the type of change in constitution that would underlie sleep disruption as a risk factor for multiple diseases. The current study was undertaken to investigate cell injury and altered cell fate as consequences of sleep deprivation, which were predicted from systemic clues. Design: Partial (35% sleep reduction) and total sleep deprivation were produced in rats for 10 days, which was tolerated and without overtly deteriorated health. Recovery rats were similarly sleep deprived for 10 days, then allowed undisturbed sleep for 2 days. The plasma, liver, lung, intestine, heart, and spleen were analyzed and compared to control values for damage to DNA, proteins, and lipids; apoptotic cell signaling and death; cell proliferation; and concentrations of glutathione peroxidase and catalase. Measurements and Results: Oxidative DNA damage in totally sleep deprived rats was 139% of control values, with organ-specific effects in the liver (247%), lung (166%), and small intestine (145%). Overall and organ-specific DNA damage was also increased in partially sleep deprived rats. In the intestinal epithelium, total sleep deprivation resulted in 5.3-fold increases in dying cells and 1.5-fold increases in proliferating cells, compared with control. Two days of recovery sleep restored the balance between DNA damage and repair, and resulted in normal or below-normal metabolic burdens and oxidative damage. Conclusions: These findings provide physical evidence that sleep loss causes cell damage, and in a manner expected to predispose to replication errors and metabolic abnormalities; thereby providing linkage between sleep loss and disease risk observed in epidemiological findings. Properties of recovery sleep include biochemical and molecular events that restore balance and decrease cell injury. Citation: Everson CA, Henchen CJ, Szabo A, Hogg N. Cell injury and repair resulting from sleep loss and sleep recovery in laboratory rats

Effect of retinoic acid on midkine gene expression in rat anterior pituitary cells.

Science.gov (United States)

Maliza, Rita; Fujiwara, Ken; Azuma, Morio; Kikuchi, Motoshi; Yashiro, Takashi

2017-06-29

Retinoic acid (RA) is converted from retinal by retinaldehyde dehydrogenases (RALDHs) and is an essential signaling molecule in embryonic and adult tissue. We previously reported that RALDH1 was produced in the rat anterior pituitary gland and hypothesized that RA was generated in the gland. Midkine (MK) is an RA-inducible growth factor, and MK production in the rat anterior pituitary gland was recently reported. However, the mechanism that regulates gene expression of MK in the pituitary gland has not been determined. To investigate regulation of MK production in the anterior pituitary gland, we analyzed changes in MK mRNA in cultured rat anterior pituitary cells. We identified MK-expressing cells by double-staining with in situ hybridization and immunohistochemical techniques for RALDH1. MK mRNA was expressed in RALDH1-producing cells in the anterior pituitary gland. Using isolated anterior pituitary cells of rats, we examined the effect of RA on gene expression of MK. Quantitative real-time PCR revealed that 72 h exposure to a concentration of 10 -6 M of retinal and all-trans retinoic acid increased MK mRNA levels by about 2-fold. Moreover, the stimulatory effect of all-trans retinoic acid was mimicked by the RA receptor agonist Am80. This is the first report to show that RA is important in regulating MK expression in rat anterior pituitary gland.

Effect of amiloride on arachidonic acid and histamine release from rat mast cells

DEFF Research Database (Denmark)

Linnebjerg, H.; Hansen, Harald S.; Jensen, B.

1989-01-01

The effect of a putative Na/H exchange inhibition on histamine and [C]arachidonic acid ([C]AA) release has been examined in rat peritoneal mast cells, using either addition of amiloride or removal of extracellular Na. The cells were stimulated by non-immunological agents, i.e. calcium ionophore A......23187, nerve growth factor (NGF), thapsigargin and compound 48/80. On the basis of the results obtained, a possible role for Na/H exchange in rat mast cell secretion is discussed....

Acquisition and Expansion of Adult Rat Bone Marrow Multipotent Mesenchymal Stromal Cells

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Šulla I.

2017-03-01

Full Text Available This study was initiated in order to test a mini-invasive method of mesenchymal stem/progenitor cells (MS/PCs isolation from a rat bone marrow (BM, and subsequently their expansion, differentiation, and evaluation of their immunophenotypic characteristics; and later their preservation as donor cells in an optimal condition for potential autotransplantation. The study group comprised of 6 adult male Sprague-Dawley (S-D rats, weighing 480—690 g. The rats were anaesthetised by isoflurane with room air in a Plexiglas box and maintained by inhalation of a mixture of isoflurane and O2. Their femurs were surgically exposed and their diaphyses double-trephined. Then BM cells were flushed out by saline with heparin and aspirated into a syringe with a solution of DMEM (Dulbecco’s modified eagle’s medium and heparin. The mononuclear cells from the BM were isolated by centrifugation and expanded in a standard culture medium supplemented with ES-FBS (es-cell-qualified foetal bovine serum, L-glutamine and rh LIF (recombinant human leukemia inhibitory factor. Following 14 days of passaging cultures, the cells were split into 2 equal parts. The first culture continued with the original medium. The second culture received additional supplementation with a human FGFβ (fibroblast growth factor beta and EGF (epidermal growth factor. The populations of these cells were analysed by light-microscopy, then the mean fluorescence intensities (MFIs of CD90 and Nestin were evaluated by a tricolour flow cytometry using monoclonal antibodies. The type of general anaesthesia used proved to be appropriate for the surgical phase of the experiments. All rats survived the harvesting of the BM without complications. The total number of mononuclear cells was 1.5—4.0 × 106 per sample and the proportion of CD90/Nestin expressing cells was < 1 %. Following 14 days of expansion, the cells became larger, adherent, with fibrillary morphology; the proportion of cells expressing

Icariin Prevents Amyloid Beta-Induced Apoptosis via the PI3K/Akt Pathway in PC-12 Cells

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Dongdong Zhang

2015-01-01

Full Text Available Icariin is a prenylated flavonol glycoside derived from the Chinese herb Epimedium sagittatum that exerts a variety of pharmacological activities and shows promise in the treatment and prevention of Alzheimer’s disease. In this study, we investigated the neuroprotective effects of icariin against amyloid beta protein fragment 25–35 (Aβ25–35 induced neurotoxicity in cultured rat pheochromocytoma PC12 cells and explored potential underlying mechanisms. Our results showed that icariin dose-dependently increased cell viability and decreased Aβ25–35-induced apoptosis, as assessed by MTT assay and Annexin V/propidium iodide staining, respectively. Results of western blot analysis revealed that the selective phosphatidylinositol 3-kinase (PI3K inhibitor LY294002 suppressed icariin-induced Akt phosphorylation, suggesting that the protective effects of icariin are associated with activation of the PI3K/Akt signaling pathway. LY294002 also blocked the icariin-induced downregulation of proapoptotic factors Bax and caspase-3 and upregulation of antiapoptotic factor Bcl-2 in Aβ25–35-treated PC12 cells. These findings provide further evidence for the clinical efficacy of icariin in the treatment of Alzheimer’s disease.

Cell renewal of glomerular cell types in normal rats. An autoradiographic analysis

International Nuclear Information System (INIS)

Pabst, R.; Sterzel, R.B.

1983-01-01

Normal adult Sprague-Dawley rats received either a single or repetitive injection of the DNA precursor 3 H-thymidine ( 3 H-TdR). For autoradiography semi-thin sections were prepared 2 hr to 14 days after labeling. The majority of labeled cells noted in glomerular tufts were endothelial cells. Mesangial cells had a lower production rate. Podocytes revealed no evidence of proliferation. Bowman's capsule cells showed a higher labeling index than tuft cells at all times. Neither the urinary nor the vascular pole was found to be a proliferative zone for Bowman's capsule cells. The flash and repetitive labeling experiments demonstrated a constant rate of cell renewal of about 1% per day, resulting in a long life span for endothelial and mesangial cells as well as Bowman's capsule cells. These data provide a basis for cell kinetic studies in models of glomerular diseases

Isolation, separation, and characterization of epithelial and connective cells from rat palate

Energy Technology Data Exchange (ETDEWEB)

Terranova, Victor Paul [Univ. of Rochester, NY (United States)

1979-01-01

Epithelial and connective tissue cells were isolated from rat palate by sequential collagenase, hyaluronidase and trypsin digestion of the extracellular matrix. Differences between the two populations were noted with respect to total cell protein, total cell water, proline uptake and incorporation, percent collagen synthesized, effects of parathyroid hormone, metabolism of D-valine and cell density. Basal epithelial cells were subsequently separated from the heterogeneous epithelial cell population on shallow linear density gradients by velocity centrifugation. The type of collagen synthesized by the basal epithelial cells was compared to the type of collagen synthesized by the connective tissue cells by means of labeled amino acid incorporation ratios. Cells isolated from the epithelial and connective tissue were compared. From these studies it can be concluded that epithelial and connective tissue cells can be isolated from rat palate as viable and distinct populations with respect to the biochemical parameters examined. Furthermore, subpopulations can be separated and biochemically characterized.

Distribution profiles of transient receptor potential melastatin- and vanilloid-related channels in rat spermatogenic cells and sperm.

Science.gov (United States)

Li, Shilin; Wang, Xinghuan; Ye, Haixia; Gao, Weicheng; Pu, Xiaoyong; Yang, Zhonghua

2010-03-01

In the present study, we aimed to investigate the expression and distribution of transient receptor potential melastatin (TRPM)- and vanilloid (TRPV)- related channels in rat spermatogenic cells and spermatozoa. Spermatogenic cells and spermatozoa were obtained from male Sprague-Dawley rats. Reverse transcription polymerase chain reaction (RT-PCR) were used to detect the expression of all TRPM and TRPV channel members with specific primers. Western blot analysis was applied for detecting the expression of TRPM and TRPV channel proteins. Immunohistochemistry staining for TRPM4, TRPM7 and TRPV5 was also performed in rat testis. The mRNAs of TRPM3, TRPM4, TRPM7 and TRPV5 were detected in the spermatogenic cells and spermatozoa in rat. Western blot analysis verified the expression of TRPM4, TRPM7 and TRPV5 in the rat spermatogenic cells and spermatozoa. Immunocytochemistry staining for TRPM and TRPV channel families indicated that TRPM4 and TRPM7 proteins were highly expressed in different stages of spermatogenic cells and spermatozoa, while TRPV5 protein was lowly expressed in these cells. Our results demonstrate that mRNAs or proteins for TRPM3, TRPM4, TRPM7 and TRPV5 exist in rat spermatogenic cells and spermatozoa. These data presented here may assist in elucidating the possible physiological function of TRPM and TRPV channels in spermatogenic cells and spermatozoa.

In vitro gamma irradiation Medical Center of leukemic cells in mice, rats, and guinea pigs

International Nuclear Information System (INIS)

Gross, L.; Dreyfuss, Y.; Ehrenreich, T.; Feldman, D.; Limbert, L.M.

1980-01-01

In vitro gamma irradiation of virus-induced (Gross) mouse leukemia cells at doses of 350 to 1600 rads (1 rad = 0.01 gray) had no effect on their ability to induce leukemia, usually within 2 weeks, after transplantation into syngeneic mice. However, when cells irradiated at doses of 2000-20,000 rads were transplanted, they induced leukemia after a latency period exceeding 2.5 months, similar to the results observed in mice inoculated with filtered mouse leukemia extracts. Similar results were also obtained after irradiation of leukemic cells derived from rats in which leukemia had been induced by rat-adapted mouse leukemia virus. Apparently, gamma irradiation at a dose of, or exceeding, 2000 rads, inhibits the ability of mouse and rat leukemic cells to induce leukemia after transplantation into syngeneic hosts; however, it does not inactivate the virus carried by such cells nor prevent it from inducing leukemia. [In previous experiments, doses of more than 4,500,000 rads were needed to inactivate the passage A (Gross) leukemia virus carried in either mouse or rat leukemic cells.] In vitro gamma irradiation of L2C guinea pig leukemic cells at doses of 750 to 2500 rads had no apparent effect on their ability to induce leukemia after transplantation into strain 2 guinea pigs. However, irradiation at doses of 3250 to 20,000 rads inactivated their ability to do so. The morphology of mouse, rat, and guinea pig leukemic cells and the virus particles present in such cells was not affected by irradiation at doses of 20,000 rads

Management of anesthesia in unspecified extra-adrenal pheochromocytoma patient who used beta-blocker

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Ayse Belin Ozer

2014-01-01

Full Text Available An operation was planned for a female patient aged 59 for intra-abdominal mass. The patient was using nebivolol for hypertension. Blood pressure (BP of the patient was raised to 200/130 mmHg during anesthesia induction. BP was gradually reduced by remifentanil infusion. Following the manipulation of the mass, BP began to increase (225/160 mmHg, thus nitroglycerin and followed nitroprusside infusion was started. Propofol (200 + 200 mg and furosemide (20 mg were administered intravenously. BP suddenly dropped (90/60 mmHg following the removal of the mass, nitroglycerine, and nitroprusside infusions were stopped; remifentanil dose was decreased and fluid was quickly infused. The patient was uneventually recovered. Vanilmandelic acid level was higher in the patient and pheochromocytoma was considered.

Formation of Cell-To-Cell Connection between Bone Marrow Cells and Isolated Rat Cardiomyocytes in a Cocultivation Model

Czech Academy of Sciences Publication Activity Database

Skopalík, J.; Pásek, Michal; Rychtárik, M.; Koristek, Z.; Gabrielová, E.; Sheer, P.; Matejovič, P.; Modrianský, M.; Klabusay, M.

2014-01-01

Roč. 5, č. 5 (2014), s. 1000185 ISSN 2157-7013 Institutional support: RVO:61388998 Keywords : bone marrow * mononuclear cells * isolated cardiomyocytes * cocultivation Subject RIV: BO - Biophysics http://omicsonline.org/ open - access /formation-of-celltocell-connection-between-bone-marrow-cells- and -isolated-rat-cardiomyocytes-2157-7013.1000185.php?aid=33364

Recipient bone marrow-derived stromal cells prolong graft survival in a rat hind limb allotransplantation model.

Science.gov (United States)

Ikeguchi, Ryosuke; Kakinoki, Ryosuke; Ohta, Souichi; Oda, Hiroki; Yurie, Hirofumi; Kaizawa, Yukitoshi; Mitsui, Hiroto; Aoyama, Tomoki; Toguchida, Junya; Matsuda, Shuichi

2017-09-01

Recent studies have indicated that bone marrow-derived stromal cells (BMSCs) have immunomodulatory properties that suppress the T cell responses that cause graft rejection. The purpose of this study is to evaluate the effect of recipient BMSCs intravenous infusion for immunomodulation in a rat vascularized composite allotransplantation model. A total of nine Wistar (WIS) rats and thirty Lewis (LEW) rats were used. BMSCs were harvested from three LEW rats. Twenty-four LEW rats were used as recipients and divided randomly into four groups: BMSC group, FK group, UT group, and Iso group. In the BMSC group, orthotopic rat hind limb transplantation was performed between WIS donor and LEW recipient rats. Recipient rats were injected intravenously with 2 × 10 6 recipient BMSCs on day 6, and with 0.2 mg/kg/day tacrolimus administered over 7 days (n = 6). In the FK group, recipient rats were treated with tacrolimus alone (n = 6). Rats in the UT group received no immunosuppressive treatment (n = 6). In the Iso group, transplantation was performed from three LEW donor rats to six LEW recipient rats without any immunosuppressive treatment (n = 6). Graft survival was assessed by daily inspection and histology. The immunological reactions of recipients were also evaluated. The graft survival of recipient rats in the BMSC group (24.5 days) was significantly prolonged in comparison with that of the FK group (18 days) (P Recipient rats in the BMSC group had significantly reduced serum IFN-γ cytokine levels (1.571 ± 0.779 pg/ml) in comparison with that of the FK group (7.059 ± 1.522 pg/ml) (P = .001). In in vitro study, BMSCs induce T cell hyporesponsiveness in a mixed lymphocyte reaction. BMSCs induce T cell hyporesponsiveness and prolong graft survival in the rat vascularized composite allotransplantation model. BMSCs exhibit immunomodulatory properties against acute rejection that can be realized without the need for significant recipient

Electrophoretic separation of cells and particles from rat pituitary and rat spleen

Science.gov (United States)

Hymer, Wesley C.

1993-01-01

There are 3 parts to the IML-2 TX-101 experiment. Part 1 is a pituitary cell culture experiment. Part 2 is a pituitary cell separation experiment using the Japanese free flow electrophoresis unit (FFEU). Part 3 is a pituitary secretory granule separation experiment using the FFEU. The objectives of this three part experiment are: (1) to determine the kinetics of production of biologically active growth hormone (GH) and prolactin (PRL) in rat pituitary GH and PRL cells in microgravity (micro-g); (2) to investigate three mechanisms by which a micro-g-induced lesion in hormone production may occur; and (3) to determine the quality of separations of pituitary cells and organelles by continuous flow electrophoresis (CFE) in micro-g under conditions where buoyancy-induced convection is eliminated.

Induction of plaque-forming cell response in adrenalectomized nude rats using Thymosin fraction 5

DEFF Research Database (Denmark)

Klausen, B; Hougen, H P; Rygaard, J

1982-01-01

In adrenalectomized nude rats treated with Thymosin fraction 5 a plaque-forming cell (PFC) response comparable to that found in normal rats was obtained. The PFC response found after adrenalectomy alone or thymosin-treatment in unoperated animals was comparable to that of untreated nude rats....

In vitro expansion and differentiation of rat pancreatic duct-derived stem cells into insulin secreting cells using a dynamicthree-dimensional cell culture system.

Science.gov (United States)

Chen, X C; Liu, H; Li, H; Cheng, Y; Yang, L; Liu, Y F

2016-06-27

In this study, a dynamic three-dimensional cell culture technology was used to expand and differentiate rat pancreatic duct-derived stem cells (PDSCs) into islet-like cell clusters that can secrete insulin. PDSCs were isolated from rat pancreatic tissues by in situ collagenase digestion and density gradient centrifugation. Using a dynamic three-dimensional culture technique, the cells were expanded and differentiated into functional islet-like cell clusters, which were characterized by morphological and phenotype analyses. After maintaining 1 x 108 isolated rat PDSCs in a dynamic three-dimensional cell culture for 7 days, 1.5 x 109 cells could be harvested. Passaged PDSCs expressed markers of pancreatic endocrine progenitors, including CD29 (86.17%), CD73 (90.73%), CD90 (84.13%), CD105 (78.28%), and Pdx-1. Following 14 additional days of culture in serum-free medium with nicotinamide, keratinocyte growth factor (KGF), and b fibroblast growth factor (FGF), the cells were differentiated into islet-like cell clusters (ICCs). The ICC morphology reflected that of fused cell clusters. During the late stage of differentiation, representative clusters were non-adherent and expressed insulin indicated by dithizone (DTZ)-positive staining. Insulin was detected in the extracellular fluid and cytoplasm of ICCs after 14 days of differentiation. Additionally, insulin levels were significantly higher at this time compared with the levels exhibited by PDSCs before differentiation (P cell culture system, PDSCs can be expanded in vitro and can differentiate into functional islet-like cell clusters.

Mast cells in lung of rat

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I. Ivanova

2017-09-01

Full Text Available This paper is a short review of scientific literature on lung mast cells in norm and pathology that shows the current state of this problem. Particular attention is paid to the quantity, location and arrangement of the mast cells. The mast cells are a part of immune system whom origin are myeloid stem cells. They are a kind of white blood cells. Many authors from the 19th century to the present day have traced and described the role of mast cells in the human body, their structure and changes depending on the functional state of the organism. Paul Ehrlich is the first author that described in his doctoral thesis the mast cells as effectors of allergy particularly in the beginning of reaction and in acute phase of the process. Research has continued through out the 20th century and researchers' efforts are primarily focused on clarifying the structure and function of mast cells and identifying their role in pathological responses in the human body. Mast cells are found in all organs, but they predominate in peripheral blood, spleen and bone marrow. There are cells in the rat skin that live for about 12 weeks, and more recent studies have found that proliferation of mature mast cells is caused by various factors.

Mitochondria-targeted antioxidant mitoquinone deactivates human and rat hepatic stellate cells and reduces portal hypertension in cirrhotic rats.

Science.gov (United States)

Vilaseca, Marina; García-Calderó, Héctor; Lafoz, Erica; Ruart, Maria; López-Sanjurjo, Cristina Isabel; Murphy, Michael P; Deulofeu, Ramon; Bosch, Jaume; Hernández-Gea, Virginia; Gracia-Sancho, Jordi; García-Pagán, Juan Carlos

2017-07-01

In cirrhosis, activated hepatic stellate cells (HSC) play a major role in increasing intrahepatic vascular resistance and developing portal hypertension. We have shown that cirrhotic livers have increased reactive oxygen species (ROS), and that antioxidant therapy decreases portal pressure. Considering that mitochondria produce many of these ROS, our aim was to assess the effects of the oral mitochondria-targeted antioxidant mitoquinone on hepatic oxidative stress, HSC phenotype, liver fibrosis and portal hypertension. Ex vivo: Hepatic stellate cells phenotype was analysed in human precision-cut liver slices in response to mitoquinone or vehicle. In vitro: Mitochondrial oxidative stress was analysed in different cell type of livers from control and cirrhotic rats. HSC phenotype, proliferation and viability were assessed in LX2, and in primary human and rat HSC treated with mitoquinone or vehicle. In vivo: CCl 4 - and thioacetamide-cirrhotic rats were treated with mitoquinone (5 mg/kg/day) or the vehicle compound, DecylTPP, for 2 weeks, followed by measurement of oxidative stress, systemic and hepatic haemodynamic, liver fibrosis, HSC phenotype and liver inflammation. Mitoquinone deactivated human and rat HSC, decreased their proliferation but with no effects on viability. In CCl 4 -cirrhotic rats, mitoquinone decreased hepatic oxidative stress, improved HSC phenotype, reduced intrahepatic vascular resistance and diminished liver fibrosis. These effects were associated with a significant reduction in portal pressure without changes in arterial pressure. These results were further confirmed in the thioacetamide-cirrhotic model. We propose mitochondria-targeted antioxidants as a novel treatment approach against portal hypertension and cirrhosis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Molecular and therapeutic advances in the diagnosis and management of malignant pheochromocytomas and paragangliomas.

LENUS (Irish Health Repository)

Lowery, Aoife J

2013-01-01

Pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare catecholamine-secreting tumors derived from chromaffin cells originating in the neural crest. These tumors represent a significant diagnostic and therapeutic challenge because the diagnosis of malignancy is frequently made in retrospect by the development of metastatic or recurrent disease. Complete surgical resection offers the only potential for cure; however, recurrence can occur even after apparently successful resection of the primary tumor. The prognosis for malignant disease is poor because traditional treatment modalities have been limited. The last decade has witnessed exciting discoveries in the study of PCCs and PGLs; advances in molecular genetics have uncovered hereditary and germline mutations of at least 10 genes that contribute to the development of these tumors, and increasing knowledge of genotype-phenotype interactions has facilitated more accurate determination of malignant potential. Elucidating the molecular mechanisms responsible for malignant transformation in these tumors has opened avenues of investigation into targeted therapeutics that show promising results. There have also been significant advances in functional and radiological imaging and in the surgical approach to adrenalectomy, which remains the mainstay of treatment for PCC. In this review, we discuss the currently available diagnostic and therapeutic options for patients with malignant PCCs and PGLs and detail the molecular rationale and clinical evidence for novel and emerging diagnostic and therapeutic strategies.

Transcription control and neuronal differentiation by agents that activate the LXR nuclear receptor family.

Science.gov (United States)

Schmidt, A; Vogel, R; Holloway, M K; Rutledge, S J; Friedman, O; Yang, Z; Rodan, G A; Friedman, E

1999-09-10

LXR and PPAR receptors belong to the nuclear receptor superfamily of transcriptional activating factors. Using ligand-dependent transcription assays, we found that 5-tetradecyloxy-2-furancarboxylic acid (TOFA) transactivates chimeric receptors composed of the glucocorticoid receptor DNA binding domain and the ligand binding regions of PPARalpha, PPARbeta (NUC-1) and LXRbeta (NER) receptors. In the same assays, ligands for PPARs (oleic acid, WY-14643 and L-631,033) and LXRs (hydroxycholesterols) maintain their respective receptor selectivity. TOFA and hydroxycholesterols also stimulate transcription from a minimal fibrinogen promoter that is under the control of AP-1 or NF-kappaB transcription factor binding sites. In addition to their effects on transcription, these LXRbeta activators induce neuronal differentiation in rat pheochromocytoma cells. TOFA and the natural LXR agonist, 22 (R)-hydroxycholesterol, stimulate neurite outgrowth in 55 and 28% of cells, respectively. No neurite outgrowth was induced by the related 22(S)-hydroxycholesterol, which does not activate the LXR family. These results suggest that the hydroxycholesterol signaling pathway has a complex effect on transcription that mediates the activity of TOFA and hydroxycholesterol on neuronal differentiation in pheochromocytoma cells.

A comparative study of myosin and its subunits in adult and neonatal-rat hearts and in rat heart cells from young and old cultures.

OpenAIRE

Ghanbari, H A; McCarl, R L

1980-01-01

A possible explanation for the decrease in myosin Ca2+-dependent ATPase activity as rat heart cells age in culture is presented. The subunit structure and enzyme kinetics of myosin from adult and neonatal rat hearts and from rat heart cells of young and old cultures are compared. These studies indicate that the loss in Ca-ATPase activity of myosin from older cultures was an intrinsic property of the myosin itself. Myofibrillar fractions from the indicated four sources showed no qualitative or...

Isolation and Osteogenic Differentiation of Rat Periosteum-derived Cells

OpenAIRE

Declercq, Heidi Andrea; De Ridder, Leo Isabelle; Cornelissen, Maria Jozefa

2005-01-01

Selection of appropriate cultures having an osteogenic potential is a necessity if cell/biomaterial interactions are studied in long-term cultures. Osteoblastic cells derived from rat long bones or calvaria have the disadvantage of being in an advanced differentiation stage which results in terminal differentiation within 21 days. In this regard, less differentiated periosteum-derived osteoprogenitors could be more suitable.

Effect of irradiation on the acinar cells of submandibular gland in streptozotocin-induced diabetic rats

International Nuclear Information System (INIS)

Lee, Seung Hyun; Hwang, Eui Hwan; Lee, Sang Rae

2003-01-01

To observe the histologic changes and clusterin expression in the acinar cells of the submandibular gland in streptozotocin-induced diabetic rat following irradiation. Mature Sprague-Dawley rats were divided into three groups: control, diabetic, and diabetic-irradiated groups. Diabetes mellitus was induced in the Sprague-Dawley rats by injecting streptozotocin, while the control rats were injected with citrate buffer only. After 5 days, rats in diabetic-irradiated group were irradiated with single absorbed dose of 10 Gy to the head and neck region. The rats were killed at 1, 3, 7, 14, 21, and 28 days after irradiation. The specimen including the submandibular gland were sectioned and observed using histologic and immunohistochemical methods. Morphologic change of acinar cells was remarkable in the diabetic group, but was not observed in the diabetic-irradiated group. Necrotic tissues were observed in the diabetic-irradiated group. Coloring of toluidine blue stain was most increased at 14 days in the diabetic group, however there were no significant change throughout the period of the experiment in the diabetic-irradiated group. Expression of clusterin was most significant at 14 days in the diabetic group, but gradually decreased with time after 7 days in the diabetic-irradiated group. Degeneration of clusterin was observed in the diabetic-irradiated group. This experiment suggests that the acinar cells of submandibular gland in rats are physiologically apoptosis by the induction of diabetes, but that the apoptosis is inhibited and the acinar cells necrotized after irradiation.

Application of rat mast cell incubates as a possible short-time test for sensitizing occupational chemicals

Energy Technology Data Exchange (ETDEWEB)

Diel, F.; Neidhart, B.; Opree, W.

1981-08-01

The direct action of sensitizing occupational chemicals (formaldehyde, phenol, phenylhydrazine, p-aminophenol) on rat mast cells was investigated by determination of histamine using HPLC separation and fluorimetric detection. It turned out that dispersed mast cells from immunized and non-immunized Wistar-rats are more sensitive than small-cut lung tissue slices. Passive cutaneous anaphylaxis was negative after a fortnight sensitizing experiment with the here described occupational chemicals. Short-time tests with rat mast cells reflect anaphylactoid response and are suitable for the screening of sensitizing chemicals.

Cell proliferation in rat nasal respiratory epithelium following three months exposure to formaldehyde gas

International Nuclear Information System (INIS)

Monticello, T.M.; Morgan, K.T.

1990-01-01

Formaldehyde (HCHO), a ubiquitous chemical and rat nasal carcinogen, enhances cell proliferation in rat, monkey, and xenotransplanted human respiratory epithelium following short-term exposure. The present studies were designed to evaluate cell proliferation in relation to tumor induction in rat nasal respiratory epithelium following subchronic HCHO exposure. Male F-344 rats were whole-body exposed to either 0, 0.7, 2, 6, 10, or 15 ppm HCHO, for wither 4 d (6hr/d), 6 wks (5d/wk) or 3 months. Animals were labeled with tritiated thymidine prior to euthanasia. Nasal sections were processed for autoradiography and cell proliferation data was expressed as unit length labeling indices (ULLI). HCHO-induced lesions and increases in cell proliferation occurred in specific regions of the nose, primarily the wall of the lateral meatus and nasal septum of the anterior nasal cavity. Following 4 d exposure, significant elevations in cell proliferation were observed only in the 6, 10 and 15 ppm groups (16-, 18-, and 20-fold increase over control, respectively). Increases in ULLI were also present in the 6, 10 and 15 ppm groups after 6 wks of exposure (12-, 35-, and 40-fold increase over control). However, after 3 months exposure, elevations in ULLI were present only in the 10 and 15 ppm groups (9- and 14-fold increase over controls). These results demonstrate that (1) low levels of HCHO (0.7 and 2 ppm) do not increase cell proliferation in rat nasal respiratory epithelium; (2) 6 ppm HCHO induces transient increases in cell proliferation; and (3) clearly carcinogenic concentrations of HCHO (10 and 15 ppm) cause sustained elevations in cell proliferation which may play an important role in HCHO-induced carcinogenesis

Effect of coffee drinking on cell proliferation in rat urinary bladder epithelium.

Science.gov (United States)

Lina, B A; Rutten, A A; Woutersen, R A

1993-12-01

A possible effect of freshly brewed drip coffee on urinary bladder carcinogenesis was investigated in male Wistar rats using cell proliferation in urinary bladder epithelium as the indicator of tumour promotion. Male rats were given either undiluted coffee brew (100% coffee), coffee diluted 10 times (10% coffee) or tap water (controls), as their only source of drinking fluid for 2 or 6 wk. Uracil, known to induce cell proliferation in urinary bladder epithelium, was included in the study as a positive control. In rats receiving 100% coffee, body weights, liquid intake and urinary volume were decreased. Neither histopathological examination of urinary bladder tissue nor the bromodeoxyuridine labelling index revealed biologically significant differences between rats receiving coffee and the tap water controls. Uracil increased the labelling index and induced hyperplasia of the urinary bladder epithelium, as expected. It was concluded that these results produced no evidence that drinking coffee predisposes to tumour development in the urinary bladder.

Adenosine formation in contracting primary rat skeletal muscle cells and endothelial cells in culture

DEFF Research Database (Denmark)

Hellsten, Ylva; Frandsen, Ulrik

1997-01-01

1. The present study examined the capacity for adenosine formation, uptake and metabolism in contracting primary rat muscle cells and in microvascular endothelial cells in culture. 2. Strong and moderate electrical simulation of skeletal muscle cells led to a significantly greater increase....... 3. Addition of microvascular endothelial cells to the cultured skeletal muscle cells enhanced the contraction-induced accumulation of extracellular adenosine (P Skeletal muscle cells were...... in the extracellular adenosine concentration (421 +/- 91 and 235 +/- 30 nmol (g protein)-1, respectively; P muscle cells (161 +/- 20 nmol (g protein)-1). The ATP concentration was lower (18%; P contracted, but not in the moderately contracted muscle cells...

Copper uptake and retention in liver parenchymal cells isolated from nutritionally copper-deficient rats

NARCIS (Netherlands)

Berg, van den G.J.; de Goeij, J.J.M.; Bock, I.; Gijbels, M.J.J.; Brouwer, A.; Lei, K.Y.; Hendriks, H.F.J.

1991-01-01

Copper uptake and retention were studied in primary cultures of liver parenchymal cells isolated from copper-deficient rats. Male Sprague-Dawley rats were fed a copper-deficient diet (<1 mg Cu/kg) for 10 wk. Copper-deficient rats were characterized by low copper concentrations in plasma and liver,

Copper uptake and retention in liver parenchymal cells isolated from nutritionally copper-deficient rats

NARCIS (Netherlands)

Berg, G.J. van den; Goeij, J.J.M. de; Bock, I.; Gijbels, M.J.J.; Brouwer, A.; Lei, K.Y.; Hendruiks, H.F.J.

1991-01-01

Copper uptake and retention were studied in primary cultures of liver parenchymal cells isolated from copper-deficient rats. Male Sprague-Dawley rats were fed a copper-deficient diet (< 1 mg Cu/kg) for 10 wk. Copper-deficient rats were characterized by low copper concentrations in plasma and liver,

Transmural changes in mast cell density in rat heart after infarct induction in vivo

NARCIS (Netherlands)

Engels, W.; Reiters, P. H.; Daemen, M. J.; Smits, J. F.; van der Vusse, G. J.

1995-01-01

The cardiac distribution of mast cells was investigated after the induction of acute myocardial infarction in the rat. The left anterior descending coronary artery (LAD) was occluded by ligation in the infarct group, whereas in sham rats only a superficial ligature was placed beside the LAD. Rats of

DNA lability induced by nimustine and ramustine in rat glioma cells.

Science.gov (United States)

Mineura, K; Fushimi, S; Itoh, Y; Kowada, M

1988-01-01

The DNA labile sites induced by two nitrosoureas, nimustine (ACNU) and ramustine (MCNU) synthesised in Japan, have been examined in highly reiterated DNA sequences of rat glioma cells. Reiterated fragments of 167 and 203 base pairs (bp), obtained after Hind III and Hae III restriction endonuclease digestion of rat glioma cells DNA, were used as target DNA sequences to determine the labile sites. In vitro reaction with ACNU and MCNU resulted in scission products corresponding to the locations of guanine. Subsequent piperidine hydrolysis produced more frequent breaks of the phosphodiester bonds at guanine positions, thus forming alkali-labile sites. Images PMID:3236017

Arthritis by autoreactive T cell lines obtained from rats after injection of intestinal bacterial cell wall fragments

NARCIS (Netherlands)

I. Klasen (Ina); J. Kool (Jeanette); M.J. Melief (Marie-José); I. Loeve (I.); W.B. van den Berg (Wim); A.J. Severijnen; M.P.H. Hazenberg (Maarten)

1992-01-01

markdownabstract__Abstract__ T cell lines (B13, B19) were isolated from the lymph nodes of Lewis rats 12 days after an arthritogenic injection of cell wall fragments of Eubacterium aerofaciens (ECW), a major resident of the human intestinal flora. These cell wall fragments consist of

Glucocorticoid-regulated and constitutive trafficking of proteolytically processed cell surface-associated glycoproteins in wild type and variant rat hepatoma cells

International Nuclear Information System (INIS)

Amacher, S.L.; Goodman, L.J.; Bravo, D.A.; Wong, K.Y.; Goldfine, I.D.; Hawley, D.M.; Firestone, G.L.

1989-01-01

Glucocorticoids regulate the trafficking of mouse mammary tumor virus (MMTV) glycoproteins to the cell surface in the rat hepatoma cell line M1.54, but not in the immunoselected sorting variant CR4. To compare the localization of MMTV glycoproteins to another proteolytically processed glycoprotein, both wild type M1.54 cells and variant CR4 cells were transfected with a human insulin receptor (hIR) expression vector, pRSVhIR. The production of cell surface hIR was monitored in dexamethasone-treated and -untreated wild type M1.54 and variant CR4 cells by indirect immunofluorescence, direct plasma membrane immunoprecipitation, and by [125I] insulin binding. In both wild type and variant rat hepatoma cells, hIR were localized at the cell surface in the presence or in the absence of 1 microM dexamethasone. In contrast, the glucocorticoid-regulated trafficking of cell surface MMTV glycoproteins occurred only in wild type M1.54 cells. We conclude that the hIR, which undergoes posttranslational processing reactions similar to MMTV glycoproteins, does not require glucocorticoids to be transported to the plasma membrane and is representative of a subset of cell surface glycoproteins whose trafficking is constitutive in rat hepatoma cells. Thus, MMTV glycoproteins and hIR provide specific cell surface markers to characterize the glucocorticoid-regulated and constitutive sorting pathways

Frequency of polyploid cells in the bone marrow of rats fed irradiated wheat

International Nuclear Information System (INIS)

George, K.P.; Chaubey, R.C.; Sundaram, K.; Gopal-Ayengar, A.R.

1976-01-01

Diets containing different proportions of non-irradiated or irradiated wheat were fed to Wistar rats for 1 or 6 wk. Cytological analysis of the bone marrow showed no significant difference in the frequency of polyploid cells in the rats fed non-irradiated or irradiated wheat diets, even when the treated wheat was fed to the rats within 24 hr of irradiation. (author)

Exploration of intrinsic and extrinsic apoptotic pathways in zearalenone-treated rat sertoli cells.

Science.gov (United States)

Xu, Ming-Long; Hu, Jin; Guo, Bao-Ping; Niu, Ya-Ru; Xiao, Cheng; Xu, Yin-Xue

2016-12-01

Zearalenone (ZEA) is a nonsteroidal estrogenic mycotoxin produced mainly by Fusarium. ZEA causes reproductive disorders and is both cytotoxic and genotoxic in animals; however, little is known regarding the molecular mechanism(s) leading to ZEA toxicity. Sertoli cells are somatic cells that support the development of spermatogenic cells. The objective of this study was to explore the effects of ZEA on the proliferation, apoptosis, and necrosis of rat Sertoli cells to uncover signaling pathways underlying ZEA cytotoxicity. ZEA reduced the proliferation of rat Sertoli cells in a dose-dependent manner, as indicated by a CCK8 assay, while flow cytometry revealed that ZEA caused both apoptosis and necrosis. Immunoblotting revealed that ZEA treatment increased the ratio of Bax/Bcl-2, as well as the expression of FasL and caspases-3, -8, and -9, in a dose-dependent manner. Collectively, these data suggest that ZEA induced apoptosis and necrosis in rat Sertoli cells via extrinsic and intrinsic apoptotic pathways. This study provides new insights into the molecular mechanisms by which ZEA exhibits cytotoxicity. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1731-1739, 2016. © 2015 Wiley Periodicals, Inc.

Elimination of acute muelogenous leukemic cells from marrow and tumor suspensions in the rat with 4-hydroperoxycyclophosphamide

International Nuclear Information System (INIS)

Sharkis, S.J.; Santos, G.W.; Colvin, M.

1980-01-01

Cell suspensions of normal rat marrow mixed with rat acute myelogenous leukemic cells were prepared and incubated in vitro with graded doses of 4-hydroperoxycyclophosphamide (4HC). The cell suspensions were injected into rats prepared with a lethal dose of total body irradiation. Animals injected with these cells survived fatal irradiation induced aplasia. In a dose related manner 4HC was able to purge tumor cells from the cell mixtures. Thus, animals given cell suspensions incubated with the lower doses of 4HC showed prolonged survived before death from leukemia and animals given cell suspensions incubated with higher doses of 4HC survival lethal irradiation without the subsequent appearance of leukemia. These studies clearly establish that tumor cells may be eliminated from normal marrow suspensions without completely destroying the pluripotent stem cells

Experimental rat lung tumor model with intrabronchial tumor cell implantation.

Science.gov (United States)

Gomes Neto, Antero; Simão, Antônio Felipe Leite; Miranda, Samuel de Paula; Mourão, Lívia Talita Cajaseiras; Bezerra, Nilfácio Prado; Almeida, Paulo Roberto Carvalho de; Ribeiro, Ronaldo de Albuquerque

2008-01-01

The objective of this study was to develop a rat lung tumor model for anticancer drug testing. Sixty-two female Wistar rats weighing 208 +/- 20 g were anesthetized intraperitoneally with 2.5% tribromoethanol (1 ml/100 g live weight), tracheotomized and intubated with an ultrafine catheter for inoculation with Walker's tumor cells. In the first step of the experiment, a technique was established for intrabronchial implantation of 10(5) to 5 x 10(5) tumor cells, and the tumor take rate was determined. The second stage consisted of determining tumor volume, correlating findings from high-resolution computed tomography (HRCT) with findings from necropsia and determining time of survival. The tumor take rate was 94.7% for implants with 4 x 10(5) tumor cells, HRCT and necropsia findings matched closely (r=0.953; p<0.0001), the median time of survival was 11 days, and surgical mortality was 4.8%. The present rat lung tumor model was shown to be feasible: the take rate was high, surgical mortality was negligible and the procedure was simple to perform and easily reproduced. HRCT was found to be a highly accurate tool for tumor diagnosis, localization and measurement and may be recommended for monitoring tumor growth in this model.

Separation of cells from the rat anterior pituitary gland

Science.gov (United States)

Hymer, W. C.; Hatfield, J. Michael

1984-01-01

Data concerned with analyzing the cellular organization of the rat anterior pituitary gland are examined. The preparation of the cell suspensions and the methods used to separate pituitary cell types are described. Particular emphasis is given to velocity sedimentation at unit gravity, density gradient centrifugation, affinity methods, fluorescence activated cell sorting, and density gradient and continuous-flow electrophoresis. The difficulties encountered when attempting to compare data from different pituitary cell separation studies are discussed, and results from various experiments are presented. The functional capabilities of the separated cell populations can be tested in various culture systems.

Transient fluctuations of intracellular zinc ions in cell proliferation

Energy Technology Data Exchange (ETDEWEB)

Li, Yuan [Division of Human Nutrition, Department of Preventive Medicine and Community Health, The University of Texas Medical Branch, Galveston, TX 77555 (United States); Maret, Wolfgang, E-mail: womaret@utmb.edu [Division of Human Nutrition, Department of Preventive Medicine and Community Health, The University of Texas Medical Branch, Galveston, TX 77555 (United States); Department of Anesthesiology, The University of Texas Medical Branch, Galveston, TX 77555 (United States)

2009-08-15

Zinc is essential for cell proliferation, differentiation, and viability. When zinc becomes limited for cultured cells, DNA synthesis ceases and the cell cycle is arrested. The molecular mechanisms of actions of zinc are believed to involve changes in the availability of zinc(II) ions (Zn{sup 2+}). By employing a fluorescent Zn{sup 2+} probe, FluoZin-3 acetoxymethyl ester, intracellular Zn{sup 2+} concentrations were measured in undifferentiated and in nerve growth factor (NGF)-differentiated rat pheochromocytoma (PC12) cells. Intracellular Zn{sup 2+} concentrations are pico- to nanomolar in PC12 cells and are higher in the differentiated than in the undifferentiated cells. When following cellular Zn{sup 2+} concentrations for 48 h after the removal of serum, a condition that is known to cause cell cycle arrest, Zn{sup 2+} concentrations decrease after 30 min but, remarkably, increase after 1 h, and then decrease again to about one half of the initial concentration. Cell proliferation, measured by an MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, decreases after both serum starvation and zinc chelation. Two peaks of Zn{sup 2+} concentrations occur within one cell cycle: one early in the G1 phase and the other in the late G1/S phase. Thus, fluctuations of intracellular Zn{sup 2+} concentrations and established modulation of phosphorylation signaling, via an inhibition of protein tyrosine phosphatases at commensurately low Zn{sup 2+} concentrations, suggest a role for Zn{sup 2+} in the control of the cell cycle. Interventions targeted at these picomolar Zn{sup 2+} fluctuations may be a way of controlling cell growth in hyperplasia, neoplasia, and diseases associated with aberrant differentiation.

Cefaléia em pacientes com feocromocitoma: influência da hipertensão arterial Headache in patients with pheochromocytoma: influence of arterial hypertension

Directory of Open Access Journals (Sweden)

ELCIO JULIATO PIOVESAN

1998-06-01

Full Text Available A cefaléia no feocromocitoma é elemento diagnóstico importante, que pode caracterizar uma reação do organismo frente a oscilações hormonais patológicas. Após averiguação da hipertensão arterial e da cefaléia em 20 pacientes durante os períodos de descompensação do feocromocitoma, sugerimos que a hipertensão arterial isolada não é o único fator desencadeante dos fenômenos álgicos cranianos. A possibilidade das variações nas catecolaminas, adrenomedulina e outras substâncias neuroendócrinas deve ser melhor esclarecida para comprovar esta hipótese.Headache is an important diagnostic element in pheochromocytoma and it may characterize a body reaction to pathological hormonal oscillations. We observed the pheochromocytoma instability in 20 patients during arterial hypertension and tried to correlate with headache. We found that isolate hypertension is not the only factor in headache pathogenesis. It is possible that changes in catecholamines, adrenomedullin and other neuropeptides may cause some of these symptoms.

Presence of stem/progenitor cells in the rat penis.

Science.gov (United States)

Lin, Guiting; Alwaal, Amjad; Zhang, Xiaoyu; Wang, Jianwen; Wang, Lin; Li, Huixi; Wang, Guifang; Ning, Hongxiu; Lin, Ching-Shwun; Xin, Zhongcheng; Lue, Tom F

2015-01-15

Tissue resident stem cells are believed to exist in every organ, and their identification is commonly done using a combination of immunostaining for putative stem cell markers and label-retaining cell (LRC) strategy. In this study, we employed these approaches to identify potential stem cells in the penis. Newborn rats were intraperitoneally injected with thymidine analog, 5-ethynyl-2-deoxyuridine (EdU), and their penis was harvested at 7 h, 3 days, 1 week, and 4 weeks. It was processed for EdU stains and immunofluorescence staining for stem cell markers A2B5, PCNA, and c-kit. EdU-positive cells were counted for each time point and co-localized with each stem cell marker, then isolated and cultured in vitro followed by their characterization using flowcytometry and immunofluorescence. At 7 h post-EdU injection, 410 ± 105.3 penile corporal cells were labeled in each cross-section (∼28%). The number of EdU-positive cells at 3 days increased to 536 ± 115.6, while their percentage dropped to 25%. Progressively fewer EdU-positive cells were present in the sacrificed rat penis at longer time points (1 and 4 weeks). They were mainly distributed in the subtunic and perisinusoidal spaces, and defined as subtunic penile progenitor cells (STPCs) and perisinusoidal penile progenitor cells (PPCs). These cells expressed c-kit, A2B5, and PCNA. After culturing in vitro, only ∼0.324% corporal cells were EdU-labeled LRCs and expressed A2B5/PCNA. Therefore, labeling of penis cells by EdU occurred randomly, and label retaining was not associated with expression of c-kit, A2B5, or PCNA. The penile LRCs are mainly distributed within the subtunic and perisinusoidal space.

Cholesterol metabolism in blood cells of irradiated rats

International Nuclear Information System (INIS)

Novoselova, E.G.; Kulagina, T.P.; Potekhina, N.I.

1985-01-01

Cholesterol metabolism in blood erythrocytes and lymphocytes of irradiated rats has been investigated. It has been found that at all terms and doses of irradiation, a suppression of the synthesis of erythrocyte cholesterol is observed. The increase of cholesterol quantiy in erythrocytes upon total gamma irradiation in the 10 Gr dose possibly is the result of growth of cholesterol transfer from plasma into erythrocyte cells. The study of the cholesterol synthesis in suspension of lymphocytes elminated from peripheral blood of control and irradiated rats has shown that at irradiation doses of 4 and 10 Gr in an hour acivation of cholesterol synthesis in vitro takes places

Intravenous grafts of amniotic fluid-derived stem cells induce endogenous cell proliferation and attenuate behavioral deficits in ischemic stroke rats.

Directory of Open Access Journals (Sweden)

Naoki Tajiri

Full Text Available We recently reported isolation of viable rat amniotic fluid-derived stem (AFS cells [1]. Here, we tested the therapeutic benefits of AFS cells in a rodent model of ischemic stroke. Adult male Sprague-Dawley rats received a 60-minute middle cerebral artery occlusion (MCAo. Thirty-five days later, animals exhibiting significant motor deficits received intravenous transplants of rat AFS cells or vehicle. At days 60-63 post-MCAo, significant recovery of motor and cognitive function was seen in stroke animals transplanted with AFS cells compared to vehicle-infused stroke animals. Infarct volume, as revealed by hematoxylin and eosin (H&E staining, was significantly reduced, coupled with significant increments in the cell proliferation marker, Ki67, and the neuronal marker, MAP2, in the dentate gyrus (DG [2] and the subventricular zone (SVZ of AFS cell-transplanted stroke animals compared to vehicle-infused stroke animals. A significantly higher number of double-labeled Ki67/MAP2-positive cells and a similar trend towards increased Ki67/MAP2 double-labeling were observed in the DG and SVZ of AFS cell-transplanted stroke animals, respectively, compared to vehicle-infused stroke animals. This study reports the therapeutic potential of AFS cell transplantation in stroke animals, possibly via enhancement of endogenous repair mechanisms.

Differences in pyrimidine dimer removal between rat skin cells in vitro and in vivo

International Nuclear Information System (INIS)

Mullaart, E.; Lohman, P.H.; Vijg, J.

1988-01-01

Pyrimidine dimers, the most abundant type of DNA lesions induced by ultraviolet light (UV), are rapidly repaired in human skin fibroblasts in vitro. In the same cell type from rats, however, there is hardly any removal of such dimers. To investigate whether this low capacity of rat skin cells to repair lesions in their DNA is an inherent characteristic of this species or an artifact due to cell culturing, we measured the removal of UV-induced pyrimidine dimers from rat epidermal keratinocytes both in vitro and in vivo. Epidermal keratinocytes in vitro were unable to remove any dimers over the first 3 h after UV-irradiation, while only about 20% was removed during a repair period of 24 h. In this respect, these cells were not different from cultured rat fibroblasts. In contrast to the results obtained with keratinocytes in vitro, we observed a rapid repair of pyrimidine dimers in UV-irradiated keratinocytes in vivo over the first 3 h; this rapid repair phase was followed by a much slower repair phase between 3 and 24 h. These results are discussed in terms of the possibility that mammalian cells are able to switch from one DNA repair pathway to another

Formation of reactive oxygen species in rat epithelial cells upon ...

Indian Academy of Sciences (India)

In our study, we investigated the influence of fly ash on the promotion of early inflammatory reactions like the formation of reactive oxygen species (ROS) in rat lung epithelial cells (RLE-6TN). Furthermore, we determined the formation of nitric oxide (NO). The cells show a clear dose-response relationship concerning the ...

Hypothiocyanite produced by human and rat respiratory epithelial cells inactivates extracellular H1N2 influenza A virus.

Science.gov (United States)

Gingerich, Aaron; Pang, Lan; Hanson, Jarod; Dlugolenski, Daniel; Streich, Rebecca; Lafontaine, Eric R; Nagy, Tamás; Tripp, Ralph A; Rada, Balázs

2016-01-01

Our aim was to study whether an extracellular, oxidative antimicrobial mechanism inherent to tracheal epithelial cells is capable of inactivating influenza H1N2 virus. Epithelial cells were isolated from tracheas of male Sprague-Dawley rats. Both primary human and rat tracheobronchial epithelial cells were differentiated in air-liquid interface cultures. A/swine/Illinois/02860/09 (swH1N2) influenza A virions were added to the apical side of airway cells for 1 h in the presence or absence of lactoperoxidase or thiocyanate. Characterization of rat epithelial cells (morphology, Duox expression) occurred via western blotting, PCR, hydrogen peroxide production measurement and histology. The number of viable virions was determined by plaque assays. Statistical difference of the results was analyzed by ANOVA and Tukey's test. Our data show that rat tracheobronchial epithelial cells develop a differentiated, polarized monolayer with high transepithelial electrical resistance, mucin production and expression of dual oxidases. Influenza A virions are inactivated by human and rat epithelial cells via a dual oxidase-, lactoperoxidase- and thiocyanate-dependent mechanism. Differentiated air-liquid interface cultures of rat tracheal epithelial cells provide a novel model to study airway epithelium-influenza interactions. The dual oxidase/lactoperoxidase/thiocyanate extracellular oxidative system producing hypothiocyanite is a fast and potent anti-influenza mechanism inactivating H1N2 viruses prior to infection of the epithelium.

Biphasic electrical targeting plays a significant role in schwann cell activation.

Science.gov (United States)

Kim, In Sook; Song, Yun Mi; Cho, Tae Hyung; Pan, Hui; Lee, Tae Hyung; Kim, Sung June; Hwang, Soon Jung

2011-05-01

Electrical stimulation (ES) is a promising technique for axonal regeneration of peripheral nerve injuries. However, long-term, continuous ES in the form of biphasic electric current (BEC) to stimulate axonal regeneration has rarely been attempted and the effects of BEC on Schwann cells are unknown. We hypothesized that long-term, continuous ES would trigger the activation of Schwann cells, and we therefore investigated the effect of BEC on the functional differentiation of primary human mesenchymal stromal cells (hMSCs) into Schwann cells, as well as the activity of primary Schwann cells. Differentiation of hMSCs into Schwann cells was determined by coculture with rat pheochromocytoma cells (PC12 cell line). We also investigated the in vivo effects of long-term ES (4 weeks) on axonal outgrowth of a severed sciatic nerve with a 7-mm gap after retraction of the nerve ends in rats by implanting an electronic device to serve as a neural conduit. PC12 cells cocultured with hMSCs electrically stimulated during culture in Schwann cell differentiation medium (Group I) had longer neurites and a greater percentage of PC12 cells were neurite-sprouting than when cocultured with hMSCs cultured in growth medium (control group) or unstimulated hMSCs in the same culture conditions as used for Group I (Group II). Group I cells showed significant upregulation of Schwann cell-related neurotrophic factors such as nerve growth factor and glial-derived neurotrophic factor compared to Group II cells at both the mRNA and protein levels. Primary Schwann cells responded to continuous BEC with increased proliferation and the induction of nerve growth factor and glial-derived neurotrophic factor, similar to Group I cells, and in addition, induction of brain-derived neurotrophic factor was observed. Immunohistochemical investigation of sciatic nerve regenerates revealed that BEC increased axonal outgrowth significantly. These results demonstrate that BEC enhanced the functional activity of

A novel rat fibrosarcoma cell line from transformed bone marrow-derived mesenchymal stem cells with maintained in vitro and in vivo stemness properties

Energy Technology Data Exchange (ETDEWEB)

Wang, Meng-Yu [Department of Cell Therapy, Institute for Cancer Research, Oslo University Hospital, Oslo (Norway); Nestvold, Janne, E-mail: j.m.nestvold@medisin.uio.no [Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo (Norway); Rekdal, Øystein [Department of Medical Biology, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø (Norway); Kvalheim, Gunnar [Department of Cell Therapy, Institute for Cancer Research, Oslo University Hospital, Oslo (Norway); Fodstad, Øystein [Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Oslo (Norway)

2017-03-15

Increasing evidence suggests a possible relationship between mesenchymal stem cells (MSCs) and sarcoma. MSCs are hypothesized to be the cells initiating sarcomagenesis, and cancer stem cells (CSCs) sharing features of MSCs have been identified in sarcomas. Here, we report on the characteristics of a bone marrow-derived rat mesenchymal stem cell line that spontaneously transformed in long-term culture. The rat transformed mesenchymal stem cells (rTMSCs) produced soft-tissue fibrosarcomas in immunocompromised mice and immunocompetent rats. In vitro, the rTMSCs displayed increased proliferation capacity compared to the untransformed cell line. The transformed MSCs maintained the mesenchymal phenotype by expression of the stem cell marker CD 90 and the lack of hematopoietic and endothelial markers. Cytogenetic analysis detected trisomy 6 in the rTMSCs. Side population (SP) isolation and tumorsphere cultivation of the transformed cells confirmed the presence of CSCs among the rTMSCs. Importantly, the rTMSCs retained their differentiation capacity towards osteogenic and adipogenic lineages. This transformed MSC-based cell line may be valuable in examining the balance in a mixed cell population between cancer stem cell properties and the ability to differentiate to specific non-transformed cell populations. Moreover, it may also be a useful tool to evaluate the efficacy of novel targeted immunotherapies in vivo. - Highlights: • Spontaneously transformed rat MSCs (rTMSCs) share characteristics with normal MSCs. • rTMSCs possess a side population, enriched with tumorigenic cells. • rTMSCs model fibrosarcoma in vivo.

A novel rat fibrosarcoma cell line from transformed bone marrow-derived mesenchymal stem cells with maintained in vitro and in vivo stemness properties

International Nuclear Information System (INIS)

Wang, Meng-Yu; Nestvold, Janne; Rekdal, Øystein; Kvalheim, Gunnar; Fodstad, Øystein

2017-01-01

Increasing evidence suggests a possible relationship between mesenchymal stem cells (MSCs) and sarcoma. MSCs are hypothesized to be the cells initiating sarcomagenesis, and cancer stem cells (CSCs) sharing features of MSCs have been identified in sarcomas. Here, we report on the characteristics of a bone marrow-derived rat mesenchymal stem cell line that spontaneously transformed in long-term culture. The rat transformed mesenchymal stem cells (rTMSCs) produced soft-tissue fibrosarcomas in immunocompromised mice and immunocompetent rats. In vitro, the rTMSCs displayed increased proliferation capacity compared to the untransformed cell line. The transformed MSCs maintained the mesenchymal phenotype by expression of the stem cell marker CD 90 and the lack of hematopoietic and endothelial markers. Cytogenetic analysis detected trisomy 6 in the rTMSCs. Side population (SP) isolation and tumorsphere cultivation of the transformed cells confirmed the presence of CSCs among the rTMSCs. Importantly, the rTMSCs retained their differentiation capacity towards osteogenic and adipogenic lineages. This transformed MSC-based cell line may be valuable in examining the balance in a mixed cell population between cancer stem cell properties and the ability to differentiate to specific non-transformed cell populations. Moreover, it may also be a useful tool to evaluate the efficacy of novel targeted immunotherapies in vivo. - Highlights: • Spontaneously transformed rat MSCs (rTMSCs) share characteristics with normal MSCs. • rTMSCs possess a side population, enriched with tumorigenic cells. • rTMSCs model fibrosarcoma in vivo.

Targeting of liposomes to cells bearing nerve growth factor receptors mediated by biotinylated NGF

International Nuclear Information System (INIS)

Rosenberg, M.B.

1986-01-01

Previous studies of liposome targeting have concentrated on immunological systems, the use of ligand-receptor interactions has received little attention. The protein hormone beta-nerve growth factor (NGF) was modified by biotinylation via carboxyl group substitution (C-bio-NGF) under reaction conditions that yielded an average of 3 biotin additions per NGF subunit. NGF was also biotinylated through amino group substitution to produce derivatives with ratios of 1, 2 and 4 biotin moieties per NGF subunit (N-bio-NGF). These derivatives were compared with native NGF for their ability to compete with 125 I-NGF for binding to NGF receptors on rat pheochromocytoma (PC 12) cells at 4 0 C. C-bio-NGF was as effective as native NGF in binding to NGF receptors, while N-bio-NGF containing 1 biotin per NGF subunit was only 28% as active in binding as native NGF. C-bio-NGF, but not N-bio-NGF, mediated the specific binding of 125 I-streptavidin to PC12 cells. Biocytin-NGF, a derivative of C-bio-NGF with an extended spacer chain, was also synthesized and retained full biological and receptor binding activities. C-bio-NGF and biocytin-NGF were as effective as native NGF in a bioassay involving induction of neurite outgrowth from PC12 cells

Motor behavioral abnormalities and histopathological findings of Wistar rats inoculated with HTLV-1-infected MT2 cells

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C.C. Câmara

2010-07-01

Full Text Available The objective of the present study was to describe motor behavioral changes in association with histopathological and hematological findings in Wistar rats inoculated intravenously with human T-cell lymphotropic virus type 1 (HTLV-1-infected MT2 cells. Twenty-five 4-month-old male rats were inoculated with HTLV-1-infected MT2 cells and 13 control rats were inoculated with normal human lymphocytes. The behavior of the rats was observed before and 5, 10, 15, and 20 months after inoculation during a 30-min/rat testing time for 5 consecutive days. During each of 4 periods, a subset of rats was randomly chosen to be sacrificed in order to harvest the spinal cord for histopathological analysis and to obtain blood for serological and molecular studies. Behavioral analyses of the HTLV-1-inoculated rats showed a significant decrease of climbing, walking and freezing, and an increase of scratching, sniffing, biting, licking, and resting/sleeping. Two of the 25 HTLV-1-inoculated rats (8% developed spastic paraparesis as a major behavioral change. The histopathological changes were few and mild, but in some cases there was diffuse lymphocyte infiltration. The minor and major behavioral changes occurred after 10-20 months of evolution. The long-term observation of Wistar rats inoculated with HTLV-1-infected MT2 cells showed major (spastic paraparesis and minor motor abnormalities in association with the degree of HTLV-1-induced myelopathy.

Dopaminergic differentiation of human neural stem cells mediated by co-cultured rat striatal brain slices

DEFF Research Database (Denmark)

Anwar, Mohammad Raffaqat; Andreasen, Christian Maaløv; Lippert, Solvej Kølvraa

2008-01-01

differentiation, we co-cultured cells from a human neural forebrain-derived stem cell line (hNS1) with rat striatal brain slices. In brief, coronal slices of neonatal rat striatum were cultured on semiporous membrane inserts placed in six-well trays overlying monolayers of hNS1 cells. After 12 days of co......Properly committed neural stem cells constitute a promising source of cells for transplantation in Parkinson's disease, but a protocol for controlled dopaminergic differentiation is not yet available. To establish a setting for identification of secreted neural compounds promoting dopaminergic...

Effects of α-particle radiation on rat tracheal epithelial cells

International Nuclear Information System (INIS)

Ford, J.R. Jr.

1992-08-01

By a combination of methods, which included flow cytometry and magnetic cell sorting, we have demonstrated that the cells of the rat tracheal epithelium which have the greatest proliferative capacity in culture and in vivo are the basal cells. Because of these findings it seems reasonable to suppose that the basal cells are the most likely target for the action of α-particle radiation in pseudostratified respiratory epithelium. This hypothesis is further supported by the finding that the basal cells are the cells which appear to respond to the tumor promoter 12-O-tetradecanoylphorbol-13-acetate. The effects of 210 Po α-particles on the survival and oncogenic transformation of rat tracheal epithelial cells in suspension were investigated. Since these effects were assayed in culture, the results pertain to the reaction of only the basal cells to irradiation. The results indicate that α-particles are extremely cytotoxic in that a track segment of 4 μm, on average, is sufficient to cause the reproductive death of basal cells. This finding is supported by similar results obtained with two cell lines, Mv1Lu and CHO-K1 BH 4 . Production of proliferating epithelial foci by α-particles was not distinguishable from control and sham treatments. These results are in direct conflict with many of the results that have been obtained with C3H 1OT1/2 cells in similar transformation assays. Some possible reasons for these disparities are discussed and supporting evidence is provided

Global demethylation of rat chondrosarcoma cells after treatment with 5-aza-2'-deoxycytidine results in increased tumorigenicity.

Directory of Open Access Journals (Sweden)

Christopher A Hamm

Full Text Available Abnormal patterns of DNA methylation are observed in several types of human cancer. While localized DNA methylation of CpG islands has been associated with gene silencing, the effect that genome-wide loss of methylation has on tumorigenesis is not completely known. To examine its effect on tumorigenesis, we induced DNA demethylation in a rat model of human chondrosarcoma using 5-aza-2-deoxycytidine. Rat specific pyrosequencing assays were utilized to assess the methylation levels in both LINEs and satellite DNA sequences following 5-aza-2-deoxycytidine treatment. Loss of DNA methylation was accompanied by an increase in invasiveness of the rat chondrosarcoma cells, in vitro, as well as by an increase in tumor growth in vivo. Subsequent microarray analysis provided insight into the gene expression changes that result from 5-aza-2-deoxycytidine induced DNA demethylation. In particular, two genes that may function in tumorigenesis, sox-2 and midkine, were expressed at low levels in control cells but upon 5-aza-2-deoxycytidine treatment these genes became overexpressed. Promoter region DNA analysis revealed that these genes were methylated in control cells but became demethylated following 5-aza-2-deoxycytidine treatment. Following withdrawal of 5-aza-2-deoxycytidine, the rat chondrosarcoma cells reestablished global DNA methylation levels that were comparable to that of control cells. Concurrently, invasiveness of the rat chondrosarcoma cells, in vitro, decreased to a level indistinguishable to that of control cells. Taken together these experiments demonstrate that global DNA hypomethylation induced by 5-aza-2-deoxycytidine may promote specific aspects of tumorigenesis in rat chondrosarcoma cells.

Light-Mediated Kinetic Control Reveals the Temporal Effect of the Raf/MEK/ERK Pathway in PC12 Cell Neurite Outgrowth

Science.gov (United States)

Zhang, Kai; Duan, Liting; Ong, Qunxiang; Lin, Ziliang; Varman, Pooja Mahendra; Sung, Kijung; Cui, Bianxiao

2014-01-01

It has been proposed that differential activation kinetics allows cells to use a common set of signaling pathways to specify distinct cellular outcomes. For example, nerve growth factor (NGF) and epidermal growth factor (EGF) induce different activation kinetics of the Raf/MEK/ERK signaling pathway and result in differentiation and proliferation, respectively. However, a direct and quantitative linkage between the temporal profile of Raf/MEK/ERK activation and the cellular outputs has not been established due to a lack of means to precisely perturb its signaling kinetics. Here, we construct a light-gated protein-protein interaction system to regulate the activation pattern of the Raf/MEK/ERK signaling pathway. Light-induced activation of the Raf/MEK/ERK cascade leads to significant neurite outgrowth in rat PC12 pheochromocytoma cell lines in the absence of growth factors. Compared with NGF stimulation, light stimulation induces longer but fewer neurites. Intermittent on/off illumination reveals that cells achieve maximum neurite outgrowth if the off-time duration per cycle is shorter than 45 min. Overall, light-mediated kinetic control enables precise dissection of the temporal dimension within the intracellular signal transduction network. PMID:24667437

Feocromocitoma bilateral: la importancia de los estudios de diagnóstico por imagen Bilateral pheochromocytoma: the importance of imaging studies

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Igor I Bonnet

2011-10-01

Full Text Available Se presenta un caso clínico poco frecuente de feocromocitoma bilateral, en el cual los estudios de diagnóstico por imagen, tanto de información estructural como funcional, constituyeron una fuente fundamental para su detección y seguimiento.We report a rare case of bilateral pheochromocytoma, in which imaging studies, both of structural and functional information, were a major source for its detection and follow-up.

Exercise reduces inflammation and cell proliferation in rat colon carcinogenesis.

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Demarzo, Marcelo Marcos Piva; Martins, Lisandra Vanessa; Fernandes, Cleverson Rodrigues; Herrero, Fábio Augusto; Perez, Sérgio Eduardo de Andrade; Turatti, Aline; Garcia, Sérgio Britto

2008-04-01

There is evidence that the risk of colon cancer is reduced by appropriate levels of physical exercise. Nevertheless, the mechanisms involved in this protective effect of exercise remain largely unknown. Inflammation is emerging as a unifying link between a range of environment exposures and neoplastic risk. The carcinogen dimethyl-hydrazine (DMH) induces an increase in epithelial cell proliferation and in the expression of the inflammation-related enzyme cyclooxigenase-2 (COX-2) in the colon of rats. Our aim was to verify whether these events could be attenuated by exercise. Four groups of eight Wistar rats were used in the experiment. The groups G1 and G3 were sedentary (controls), and the groups G2 and G4 were submitted to 8 wk of swimming training, 5 d.wk. The groups G3 and G4 were given subcutaneous injections of DMH immediately after the exercise protocols. Fifteen days after the neoplasic induction, the rats were sacrificed and the colon was processed for histological examination and immunohistochemistry staining of proliferating cell nuclear antigen (PCNA) and COX-2. We found a significant increase in the PCNA-labeling index in both DMH-treated groups of rats. However, this increase was significantly attenuated in the training group G4 (P < 0.01). Similar results were observed in relation to the COX-2 expression. From our findings, we conclude that exercise training exerts remarkable antiproliferative and antiinflammatory effects in the rat colonic mucosa, suggesting that this may be an important mechanism to explain how exercise protects against colonic cancer.

Circulating blocking factors of lymphoid-cell cytotoxicity in x-ray-induced rat small-bowel adenocarcinoma

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