WorldWideScience

Sample records for ngf-differentiated rat pheochromocytoma

  1. Antinociceptive Effect of Intrathecal Microencapsulated Human Pheochromocytoma Cell in a Rat Model of Bone Cancer Pain

    Directory of Open Access Journals (Sweden)

    Xiao Li

    2014-07-01

    Full Text Available Human pheochromocytoma cells, which are demonstrated to contain and release met-enkephalin and norepinephrine, may be a promising resource for cell therapy in cancer-induced intractable pain. Intrathecal injection of alginate-poly (l lysine-alginate (APA microencapsulated human pheochromocytoma cells leads to antinociceptive effect in a rat model of bone cancer pain, and this effect was blocked by opioid antagonist naloxone and alpha 2-adrenergic antagonist rauwolscine. Neurochemical changes of cerebrospinal fluid are in accordance with the analgesic responses. Taken together, these data support that human pheochromocytoma cell implant-induced antinociception was mediated by met-enkephalin and norepinephrine secreted from the cell implants and acting at spinal receptors. Spinal implantation of microencapsulated human pheochromocytoma cells may provide an alternative approach for the therapy of chronic intractable pain.

  2. Mechanism of palytoxin-induced [3H]norepinephrine release from a rat pheochromocytoma cell line

    International Nuclear Information System (INIS)

    Tatsumi, M.; Takahashi, M.; Ohizumi, Y.

    1984-01-01

    Palytoxin, isolated from the zoanthid Palytoha species, is one of the most potent marine toxins. Palytoxin caused a release of [ 3 H]norepinephrine from clonal rat pheochromocytoma cells in a concentration-dependent manner. This releasing action of palytoxin was markedly inhibited or abolished by Co 2+ or Ca 2+ -free medium, but was not modified by tetrodotoxin. The release of [ 3 H]norepinephrine induced by a low concentration of palytoxin was abolished in sodium-free medium and increased as the external Na+ concentrations were increased, but the release induced by a high concentration was unaffected by varying the concentration of external Na + . The release of [ 3 H]norepinephrine induced by both concentrations of palytoxin increased with increasing Ca 2+ concentrations. Palytoxin caused a concentration-dependent increase in 22 Na and 45 Ca influxes into pheochromocytoma cells. The palytoxin-induced 45 Ca influx was markedly inhibited by Co 2+ , whereas the palytoxin-induced 22 Na influx was not affected by tetrodotoxin. These results suggest that in pheochromocytoma cells the [ 3 H]norepinephrine release induced by lower concentrations of palytoxin is primarily brought about by increasing tetrodotoxin-insensitive Na + permeability across the cell membrane, whereas that induced by higher concentrations is mainly caused by a direct increase in Ca 2+ influx into them

  3. Mechanism of palytoxin-induced [3H]norepinephrine release from a rat pheochromocytoma cell line.

    Science.gov (United States)

    Tatsumi, M; Takahashi, M; Ohizumi, Y

    1984-05-01

    Palytoxin, isolated from the zoanthid Palytoha species, is one of the most potent marine toxins. Palytoxin (1 nM-1 microM) caused a release of [3H]norepinephrine from clonal rat pheochromocytoma cells in a concentration-dependent manner. This releasing action of palytoxin was markedly inhibited or abolished by Co2+ or Ca2+ -free medium, but was not modified by tetrodotoxin. The release of [3H]norepinephrine induced by a low concentration (30 nM) of palytoxin was abolished in sodium-free medium and increased as the external Na+ concentrations were increased from 3 to 100 nM, but the release induced by a high concentration (1 microM) was unaffected by varying the concentration of external Na+ from 0 to 100 mM. The release of [3H]norepinephrine induced by both concentrations of palytoxin increased with increasing Ca2+ concentrations from 0 to 3 mM. Palytoxin caused a concentration-dependent increase in 22Na and 45Ca influxes into pheochromocytoma cells at concentrations of 0.1 nM-10 nM and 1 nM-1 microM, respectively. The palytoxin-induced 45Ca influx was markedly inhibited by Co2+, whereas the palytoxin-induced 22Na influx was not affected by tetrodotoxin. These results suggest that in pheochromocytoma cells the [3H]norepinephrine release induced by lower concentrations of palytoxin is primarily brought about by increasing tetrodotoxin-insensitive Na+ permeability across the cell membrane, whereas that induced by higher concentrations is mainly caused by a direct increase in Ca2+ influx into them.

  4. Quantitative determination of dopamine in single rat pheochromocytoma cells by microchip electrophoresis with only one high-voltage power supply.

    Science.gov (United States)

    Sha, Cuicui; Fan, Yuejuan; Cheng, Jieke; Cheng, Han

    2015-07-01

    We developed a method for the direct identification of dopamine in single cultured rat pheochromocytoma cells by capillary electrophoresis using an end-channel carbon fiber nanoelectrode amperometric detector. The operation mode was designed to achieve single-cell injection and lysis in microfluidic chip electrophoresis with only one high-voltage power supply. The separation and detection conditions were optimized. Four catecholamines were baseline-separated and determined with this system, and the cell density and liquid height of the reservoirs were accommodated for single cell loading, docking and analysis. The microchip capillary electrophoresis system was successfully applied to determine dopamine in single cultured rat pheochromocytoma cells. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Mechanism of palytoxin-induced (/sup 3/H)norepinephrine release from a rat pheochromocytoma cell line

    Energy Technology Data Exchange (ETDEWEB)

    Tatsumi, M.; Takahashi, M.; Ohizumi, Y.

    1984-05-01

    Palytoxin, isolated from the zoanthid Palytoha species, is one of the most potent marine toxins. Palytoxin caused a release of (/sup 3/H)norepinephrine from clonal rat pheochromocytoma cells in a concentration-dependent manner. This releasing action of palytoxin was markedly inhibited or abolished by Co/sup 2 +/ or Ca/sup 2 +/ -free medium, but was not modified by tetrodotoxin. The release of (/sup 3/H)norepinephrine induced by a low concentration of palytoxin was abolished in sodium-free medium and increased as the external Na+ concentrations were increased, but the release induced by a high concentration was unaffected by varying the concentration of external Na/sup +/. The release of (/sup 3/H)norepinephrine induced by both concentrations of palytoxin increased with increasing Ca/sup 2 +/ concentrations. Palytoxin caused a concentration-dependent increase in /sup 22/Na and /sup 45/Ca influxes into pheochromocytoma cells. The palytoxin-induced /sup 45/Ca influx was markedly inhibited by Co/sup 2 +/, whereas the palytoxin-induced /sup 22/Na influx was not affected by tetrodotoxin. These results suggest that in pheochromocytoma cells the (/sup 3/H)norepinephrine release induced by lower concentrations of palytoxin is primarily brought about by increasing tetrodotoxin-insensitive Na/sup +/ permeability across the cell membrane, whereas that induced by higher concentrations is mainly caused by a direct increase in Ca/sup 2 +/ influx into them.

  6. Essential Oils from the Medicinal Herbs Upregulate Dopamine Transporter in Rat Pheochromocytoma Cells.

    Science.gov (United States)

    Choi, Min Sun; Choi, Bang-sub; Kim, Sang Heon; Pak, Sok Cheon; Jang, Chul Ho; Chin, Young-Won; Kim, Young-Mi; Kim, Dong-il; Jeon, Songhee; Koo, Byung-Soo

    2015-10-01

    The dopamine transporter (DAT) protein, a component of the dopamine system, undergoes adaptive neurobiological changes from drug abuse. Prevention of relapse and reduction of withdrawal symptoms are still the major limitations in the current pharmacological treatments of drug addiction. The present study aimed to investigate the effects of essential oils extracted from Elsholtzia ciliata, Shinchim, Angelicae gigantis Radix, and Eugenia caryophyllata, well-known traditional Korean medicines for addiction, on the modulation of dopamine system in amphetamine-treated cells and to explore the possible mechanism underlying its therapeutic effect. The potential cytotoxic effect of essential oils was evaluated in PC12 rat pheochromocytoma cells using cell viability assays. Quantification of DAT, p-CREB, p-MAPK, and p-Akt was done by immunoblotting. DAT was significantly reduced in cells treated with 50 μM of amphetamine in a time-dependent manner. No significant toxicity of essential oils from Elsholtzia ciliata and Shinchim was observed at doses of 10, 25, and 50 μg/mL. However, essential oils from A. gigantis Radix at a dose of 100 μg/mL and E. caryophyllata at doses of 50 and 100 μg/mL showed cytotoxicity. Treatment with GBR 12909, a highly selective DAT inhibitor, significantly increased DAT expression compared with that of amphetamine only by enhancing phosphorylation of mitogen-activated protein kinases (MAPK) and Akt. In addition, essential oils effectively induced hyperphosphorylation of cyclic-AMP response element-binding protein (CREB), MAPK, and Akt, which resulted in DAT upregulation. Our study implies that the essential oils may rehabilitate brain dopamine function through increased DAT availability in abstinent former drug users.

  7. [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.

  8. Toxic effect of zinc nanoscale metal-organic frameworks on rat pheochromocytoma (PC12) cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Ren, Fei, E-mail: paper_mail@126.com [Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou 510515 (China); Yang, Baochun; Cai, Jing [Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou 510515 (China); Jiang, Yaodong [Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou 510515 (China); Xu, Jun [Department of Health Economy Administration, Nanfang Hospital, Southern Medical University, Guangzhou 510515 (China); Wang, Shan [Department of Pharmacy, Winthrop University Hospital, Mineola, NY 11501 (United States)

    2014-04-01

    Highlights: • Metal-organic frameworks (MOFs) represent a newborn family of hybrid materials. • MOFs have already shown promise in a number of biological applications. • The biological applications of MOFs raise concerns for potential cytotoxicity. • Substantial information about MOF's neurotoxicity is still quite scarce. • This study reveals for the first time the interaction of MOFs with neural cells. - Abstract: Metal-organic frameworks (MOFs) possess unique properties desirable for delivery of drugs and gaseous therapeutics, but their uncharacterized interactions with cells raise increasing concerns of their safety in such biomedical applications. We evaluated the adverse effects of zinc nanoscale MOFs on the cell morphology, cytoskeleton, cell viability and expression of neurotrophin signaling pathway-associated GAP-43 protein in rat pheochromocytoma PC12 cells. At the concentration of 25 μg/ml, zinc MOFs did not significantly affect morphology, viability and membrane integrity of the cells. But at higher concentrations (over 100 μg/ml), MOFs exhibited a time- and concentration-dependent cytotoxicity, indicating their entry into the cells via endocytosis where they release Zn{sup 2+} into the cytosol to cause increased intracellular concentration of Zn{sup 2+}. We demonstrated that the toxicity of MOFs was associated with a disrupted cellular zinc homeostasis and down-regulation of GAP-43 protein, which might be the underlying mechanism for the improved differentiation in PC12 cells. These findings highlight the importance of cytotoxic evaluation of the MOFs before their biomedical application.

  9. MECHANISMS OF MANGANESE-INDUCED RAT PHEOCHROMOCYTOMA (PC12) CELL DEATH AND CELL DIFFERENTIATION. (R826248)

    Science.gov (United States)

    Mn is a neurotoxin that leads to a syndrome resembling Parkinson's disease after prolonged exposure to high concentrations. Our laboratory has been investigating the mechanism by which Mn induces neuronal cell death. To accomplish this, we have utilized rat pheochromocytom...

  10. Endosomes and lysosomes are involved in early steps of Tl(III)-mediated apoptosis in rat pheochromocytoma (PC12) cells.

    Science.gov (United States)

    Hanzel, Cecilia E; Almeira Gubiani, María F; Verstraeten, Sandra V

    2012-11-01

    The mechanisms that mediate thallium (Tl) toxicity are still not completely understood. The exposure of rat pheochromocytoma (PC12) cells to Tl(I) or Tl(III) activates both mitochondrial (Tl(I) and Tl(III)) and extrinsic (Tl(III)) pathways of apoptosis. In this work we evaluated the hypothesis that the effects of Tl(III) may be mediated by the damage to lysosomes, where it might be incorporated following the route of iron uptake. PC12 cells exposed for 3 h to 100 μM Tl(III) presented marked endosomal acidification, effect that was absent when cells were incubated in a serum-free medium and that was fully recovered when the latter was supplemented with transferrin. After 6 h of incubation the colocalization of cathepsins D and B with the lysosomal marker Lamp-1 was decreased together with an increase in the total activity of the enzymes. A permanent damage to lysosomes after 18 h of exposure was evidenced from the impairment of acridine orange uptake. Cathepsin D caused the cleavage of pro-apoptotic protein BID that is involved in the activation of the intrinsic pathway of apoptosis. Supporting that, BID cleavage and the activation of caspase 3 by Tl(III) were fully prevented when cells were preincubated with cathepsin D inhibitor (pepstatin A) and only partially prevented when cathepsin B inhibitor (E64d) was used. None of these inhibitors affected BID cleavage or caspase 3 activation in Tl(I)-treated cells. Together, experimental results support the role of Tl(III) uptake by the acidic cell compartments and their involvement in the early steps of Tl(III)-mediated PC12 cells apoptosis.

  11. Human placental eXpanded (PLX) mesenchymal-like adherent stromal cells confer neuroprotection to nerve growth factor (NGF)-differentiated PC12 cells exposed to ischemia by secretion of IL-6 and VEGF.

    Science.gov (United States)

    Lahiani, Adi; Zahavi, Efrat; Netzer, Nir; Ofir, Racheli; Pinzur, Lena; Raveh, Shani; Arien-Zakay, Hadar; Yavin, Ephraim; Lazarovici, Philip

    2015-02-01

    Mesenchymal stem cells are potent candidates in stroke therapy due to their ability to secrete protective anti-inflammatory cytokines and growth factors. We investigated the neuroprotective effects of human placental mesenchymal-like adherent stromal cells (PLX) using an established ischemic model of nerve growth factor (NGF)-differentiated pheochromocytoma PC12 cells exposed to oxygen and glucose deprivation (OGD) followed by reperfusion. Under optimal conditions, 2 × 10⁵ PLX cells, added in a trans-well system, conferred 30-60% neuroprotection to PC12 cells subjected to ischemic insult. PC12 cell death, measured by LDH release, was reduced by PLX cells or by conditioned medium derived from PLX cells exposed to ischemia, suggesting the active release of factorial components. Since neuroprotection is a prominent function of the cytokine IL-6 and the angiogenic factor VEGF165, we measured their secretion using selective ELISA of the cells under ischemic or normoxic conditions. IL-6 and VEGF165 secretion by co-culture of PC12 and PLX cells was significantly higher under ischemic compared to normoxic conditions. Exogenous supplementation of 10 ng/ml each of IL-6 and VEGF165 to insulted PC12 cells conferred neuroprotection, reminiscent of the neuroprotective effect of PLX cells or their conditioned medium. Growth factors as well as co-culture conditioned medium effects were reduced by 70% and 20% upon pretreatment with 240 ng/ml Semaxanib (anti VEGF165) and/or 400 ng/ml neutralizing anti IL-6 antibody, respectively. Therefore, PLX-induced neuroprotection in ischemic PC12 cells may be partially explained by IL-6 and VEGF165 secretion. These findings may also account for the therapeutic effects seen in clinical trials after treatment with these cells. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Pleurotus giganteus (Berk.) Karunarathna & K.D. Hyde: Nutritional value and in vitro neurite outgrowth activity in rat pheochromocytoma cells.

    Science.gov (United States)

    Phan, Chia-Wei; Wong, Wei-Lun; David, Pamela; Naidu, Murali; Sabaratnam, Vikineswary

    2012-07-19

    Drugs dedicated to alleviate neurodegenerative diseases like Parkinson's and Alzheimer's have always been associated with debilitating side effects. Medicinal mushrooms which harness neuropharmacological compounds offer a potential possibility for protection against such diseases. Pleurotus giganteus (formerly known as Panus giganteus) has been consumed by the indigenous people in Peninsular Malaysia for many years. Domestication of this wild mushroom is gaining popularity but to our knowledge, medicinal properties reported for this culinary mushroom are minimal. The fruiting bodies P. giganteus were analysed for its nutritional values. Cytotoxicity of the mushroom's aqueous and ethanolic extracts towards PC12, a rat pheochromocytoma cell line was assessed by using 3-[4,5-dimethythiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. Neurite outgrowth stimulation assay was carried out with nerve growth factor (NGF) as control. To elucidate signaling mechanisms involved by mushroom extract-induced neurite outgrowth, treatment of specific inhibitor for MEK/ERK and PI3K signalling pathway was carried out. The fruiting bodies of P. giganteus were found to have high carbohydrate, dietary fibre, potassium, phenolic compounds and triterpenoids. Both aqueous and ethanolic extracts induced neurite outgrowth of PC12 cells in a dose- and time-dependant manner with no detectable cytotoxic effect. At day 3, 25 μg/ml of aqueous extract and 15 μg/ml of ethanolic extract showed the highest percentage of neurite-bearing cells, i.e. 31.7 ± 1.1% and 33.3 ± 0.9%; respectively. Inhibition treatment results suggested that MEK/ERK and PI3K/Akt are responsible for neurite outgrowth of PC12 cells stimulated by P. giganteus extract. The high potassium content (1345.7 mg/100 g) may be responsible for promoting neurite extension, too. P. giganteus contains bioactive compounds that mimic NGF and are responsible for neurite stimulation. Hence, this mushroom may be

  13. Interleukin-22 protects rat PC12 pheochromocytoma cells from serum deprivation-induced cell death.

    Science.gov (United States)

    Liu, Yongchun; Pan, Wenyan; Yang, Shengmei; Wu, Xiaoying; Wu, Jianfu; Ma, Jun; Yuan, Zengqiang; Meng, Songshu

    2012-12-01

    Interleukin-22 (IL-22), an IL-10 family cytokine, mediates the crosstalk between leukocytes and epithelial cells. Previous studies reported that IL-22 expresses in mouse brain, and the rat PC12 cells are responsive to IL-22 stimulation. However, the biological roles of IL-22 in neuronal cells remain largely unknown. We show here that IL-22 activates Stat3, p38 mitogen-activated protein kinases (MAPK), and Akt pathways and inhibits Erk/MAPK pathway in naïve PC12 cells. We further demonstrate that IL-22 protects naïve PC12 cells from serum starvation-induced cell death via the Jak1/Stat3 and Akt pathways. We also show that IL-22 has no effects on naïve PC12 cell proliferation and cannot protect naïve PC12 cells from 1-methyl-4-phenylpyridinium (MPP(+))-induced cytotoxicity. However, IL-22 exerts a dose-dependent protective effect on MPP(+)-induced neurodegeneration in nerve growth factor-differentiated PC12 cells. Overall, our data suggest that IL-22 might play a role in neurological processes. To our knowledge, this is the first report showing that IL-22 confers a neuroprotective function, which may provide a new therapeutic option for treatment of neurodegenerative diseases.

  14. Pheochromocytoma and Paraganglioma: Overview

    Science.gov (United States)

    ... African Americans. Sex Pheochromocytomas occur equally in both males and females. Age Pheochromocytomas can occur at any age, although the most frequent age is between 30 and 50s. Overview Content Tools ThemeBuilder Activity Home Accessibility Contact Disclaimer Privacy Policy ...

  15. 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...

  16. Unusual presentation of pheochromocytoma

    Directory of Open Access Journals (Sweden)

    Rajendra B. Nerli

    2014-01-01

    Full Text Available Pheochromocytomas are rare catecholamine-secreting tumors that arise from chromaffin tissue within the adrenal medulla and extra-adrenal sites. Due to the excess secretion of hormones, these tumors often cause debilitating symptoms and a poor quality-of-life. Although medical management plays a significant role in the treatment of pheochromocytoma patients, surgical excision remains the only cure. Pheochromocytoma usually has three classic symptoms-headache, sweating and heart palpitations (a fast heart beat in association with markedly elevated blood pressure (hypertension. Hormones such as catecholamines and metanephrines are measured in a 24 h urine collection and metanephrines may also be measured in the blood, to make a diagnosis of pheochromocytoma. If these are greater than 2 times the normal level, imaging studies are usually done to look at the adrenal glands. We report on three cases of pheochromocytoma, which had unusual presentation.

  17. Pheochromocytoma during Pregnancy

    Science.gov (United States)

    ... of the MIBG. Octreotide scan : A type of radionuclide scan used to find certain tumors, including tumors ... cause signs or symptoms are treated with drug therapy. Drug therapy begins when pheochromocytoma or paraganglioma is ...

  18. Perioperative Management of Pheochromocytoma.

    Science.gov (United States)

    Naranjo, Julian; Dodd, Sarah; Martin, Yvette N

    2017-08-01

    Pheochromocytomas are rare neuroendocrine tumors that produce and store catecholamines. Without adequate preparation, the release of excessive amounts of catecholamines, especially during anesthetic induction or during surgical removal, can produce life-threatening cardiovascular complications. This review focuses on the perioperative management of pheochromocytoma/paragangliomas, initially summarizing the clinical aspects of the disease and then highlighting the current evidence available for preoperative, intraoperative, and postoperative anesthetic management. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Hypertensive crisis secondary to pheochromocytoma.

    Science.gov (United States)

    Greenleaf, Christopher E; Griffin, Laura A; Shake, Jay G; Orr, Wayne S

    2017-07-01

    Pheochromocytoma is an uncommon tumor of the adrenal glands that can present with headaches, sweating, palpitations, and paroxysmal hypertension. Pheochromocytoma crisis can lead to cardiomyopathy, pulmonary edema, and even total circulatory collapse. We describe a patient with hypoxic respiratory failure requiring extracorporeal membrane oxygenation to stabilize until the pheochromocytoma was discovered and treated.

  20. Tl(I) and Tl(III) activate both mitochondrial and extrinsic pathways of apoptosis in rat pheochromocytoma (PC12) cells.

    Science.gov (United States)

    Hanzel, Cecilia Eliana; Verstraeten, Sandra Viviana

    2009-04-01

    Thallium (Tl) is a highly toxic metal though yet its mechanisms are poorly understood. Previously, we demonstrated that rat pheochromocytoma (PC12) cells exposure to thallous (Tl(I)) or thallic (Tl(III)) cations leads to mitochondrial damage and reduced cell viability. In the present work we comparatively characterized the possible pathways involved in Tl(I)- and Tl(III)- (10-100 muM) mediated decrease in PC12 cells viability. We observed that these cations do not cause cell necrosis but significantly increased the number of cells with apoptotic features. Both cations lead to Bax oligomerization and caused apoptosis inducing factor (AIF), endonuclease G (Endo G), and cytochrome c release from mitochondria, but they did not activate caspase dependent DNAse (CAD). Tl(I)- and Tl(III)-dependent caspases 9 and 3 activation followed similar kinetics, with maximal effects at 18 h of incubation. In addition, Tl(I) promoted phosphatidylserine (PS) exposure. Tl(III) induced 2- and 18-fold increase in Fas content and caspase 8 activity, respectively. Together, experimental results show that Tl(I) and Tl(III) induce PC12 cells apoptosis, although differential pathways are involved. While Tl(I)-mediated cell apoptosis was mainly associated with mitochondrial damage, Tl(III) showed a mixed effect triggering both the intrinsic and extrinsic pathways of apoptosis. These findings contribute to a better understanding of the mechanisms underlying Tl-induced loss of cell viability in PC12 cells.

  1. Evolution of a pheochromocytoma.

    Science.gov (United States)

    Magill, Steven B; Fritsche, Claire M; Klinger, Dean E; Tector, Alfred J; Shaker, Joseph L

    2006-01-01

    To present a case that demonstrates the evolution of a pheochromocytoma over a several-year period and to emphasize the importance of a thorough work-up for pheochromocytoma in patients with neurofibromatosis type 1 (NF1) and hypertension. We review the long-term clinical, biochemical, and imaging findings in a man with a complex medical history of hypertension, NF1, and cardiomyopathy. A 44-year-old man, with a well-documented history of headaches, hypertension, and NF1, was referred for evaluation of a right adrenal enlargement. He had developed cardiomyopathy and undergone an evaluation for cardiac transplantation. Initial computed tomography revealed subtle asymmetry in the upper right adrenal gland. Biochemical studies for pheochromocytoma yielded equivocal findings, with a 1.5-fold elevation in the urinary norepinephrine and near-normal urinary metanephrine level. Because 131I-metaiodobenzylguanidine imaging showed no tracer uptake in the area of the right adrenal gland, the patient was thought not to have a pheochromocytoma. The patient eventually underwent cardiac transplantation and did well. On reassessment 3 1/2 years later, he was found to have a larger right adrenal mass. The second endocrine evaluation demonstrated substantial elevation in the urinary metanephrine level, and the patient underwent laparoscopic right adrenalectomy to remove the tumor (3.5 by 3.0 by 2.5 cm), which proved to be a pheochromocytoma. This case shows that a pheochromocytoma can be difficult to diagnose and can evolve to become a large, biochemically active tumor. It is imperative that patients with an adrenal tumor undergo periodic reevaluation to ensure that the tumor remains stable in size. If the tumor enlarges, further biochemical testing is warranted.

  2. RabGEF1/Rabex-5 Regulates TrkA-Mediated Neurite Outgrowth and NMDA-Induced Signaling Activation in NGF-Differentiated PC12 Cells

    Science.gov (United States)

    Tam, See-Ying; Lilla, Jennifer N.; Chen, Ching-Cheng; Kalesnikoff, Janet; Tsai, Mindy

    2015-01-01

    Nerve growth factor (NGF) binds to its cognate receptor TrkA and induces neuronal differentiation by activating distinct downstream signal transduction events. RabGEF1 (also known as Rabex-5) is a guanine nucleotide exchange factor for Rab5, which regulates early endosome fusion and vesicular trafficking in endocytic pathways. Here, we used the antisense (AS) expression approach to induce an NGF-dependent sustained knockdown of RabGEF1 protein expression in stable PC12 transfectants. We show that RabGEF1 is a negative regulator of NGF-induced neurite outgrowth and modulates other cellular and signaling processes that are activated by the interaction of NGF with TrkA receptors, such as cell cycle progression, cessation of proliferation, and activation of NGF-mediated downstream signaling responses. Moreover, RabGEF1 can bind to Rac1, and the activation of Rac1 upon NGF treatment is significantly enhanced in AS transfectants, suggesting that RabGEF1 is a negative regulator of NGF-induced Rac1 activation in PC12 cells. Furthermore, we show that RabGEF1 can also interact with NMDA receptors by binding to the NR2B subunit and its associated binding partner SynGAP, and negatively regulates activation of nitric oxide synthase activity induced by NMDA receptor stimulation in NGF-differentiated PC12 cells. Our data suggest that RabGEF1 is a negative regulator of TrkA-dependent neuronal differentiation and of NMDA receptor-mediated signaling activation in NGF-differentiated PC12 cells. PMID:26588713

  3. Nrdp1 Increases Ischemia Induced Primary Rat Cerebral Cortical Neurons and Pheochromocytoma Cells Apoptosis Via Downregulation of HIF-1α Protein

    Directory of Open Access Journals (Sweden)

    Yuan Zhang

    2017-09-01

    Full Text Available Neuregulin receptor degradation protein-1 (Nrdp1 is an E3 ubiquitin ligase that targets proteins for degradation and regulates cell growth, apoptosis and oxidative stress in various cell types. We have previously shown that Nrdp1 is implicated in ischemic cardiomyocyte death. In this study, we investigated the change of Nrdp1 expression in ischemic neurons and its role in ischemic neuronal injury. Primary rat cerebral cortical neurons and pheochromocytoma (PC12 cells were infected with adenoviral constructs expressing Nrdp1 gene or its siRNA before exposing to oxygen-glucose deprivation (OGD treatment. Our data showed that Nrdp1 was upregulated in ischemic brain tissue 3 h after middle cerebral artery occlusion (MCAO and in OGD-treated neurons. Of note, Nrdp1 overexpression by Ad-Nrdp1 enhanced OGD-induced neuron apoptosis, while knockdown of Nrdp1 with siRNA attenuated this effect, implicating a role of Nrdp1 in ischemic neuron injury. Moreover, Nrdp1 upregulation is accompanied by increased protein ubiquitylation and decreased protein levels of ubiquitin-specific protease 8 (USP8 in OGD-treated neurons, which led to a suppressed interaction between USP8 and HIF-1α and subsequently a reduction in HIF-1α protein accumulation in neurons under OGD conditions. In conclusion, our data support an important role of Nrdp1 upregulation in ischemic neuronal death, and suppressing the interaction between USP8 and HIF-1α and consequently the hypoxic adaptive response of neurons may account for this detrimental effect.

  4. Pheochromocytoma and paraganglioma

    International Nuclear Information System (INIS)

    Reckova, M.

    2013-01-01

    Pheochromocytoma and paraganglioma are rare tumors that originate from the cells of neural crest. Despite a wide variety of clinical features, the main remains the hypertension. Most of pheochromocytoma (FEO) and paraganglioma (PGL) represent sporadic tumors but about 20-30% of these tumors are familial. Besides standard imagining techniques, functional diagnostics plays important role, as well. The definitive treatment is surgical therapy, however in inoperable cases, radionuclide therapeutic methods are used. Systemic chemotherapy has only limited efficacy and, currently, targeted therapeutic approaches are studied. External-beam radiotherapy is used in palliative settings. The most frequent causes of morbidity and mortality are cardiovascular events, such as sudden death, heart attack, heart failure and cerebrovascular events. Early diagnosis is very important not just for prevention of disease dissemination, but for the prevention of possible complications, as well. (author)

  5. Investigation of amyloid formation inhibition of chemically and biogenically from Citrus aurantium L. blossoms and Rose damascena oils of gold nanoparticles: Toxicity evaluation in rat pheochromocytoma PC12 cells.

    Science.gov (United States)

    Sattarahmady, N; Firoozabadi, V; Nazari-Vanani, R; Azarpira, N

    2018-02-06

    Fibrillation inhibition effects of chemically and biogenically gold nanoparticles (GNPs) were investigated in vitro using human insulin as a model for fibrillation of protein. This inspection was followed using the Congo red assay, thioflavin T fluorescence measurements, transmission electron microscopy, and evaluation of cytotoxicity effects on rat pheochromocytoma PC12 cells. Biogenic GNPs were synthesized using oil extracts of Citrus aurantium L. blossoms and Rose damascena blossoms as reducing and concomitant agents. Congo red assay showed development of fibril formation of insulin at acidic media at 60°C over a period of 48h. In these circumstances, transmission electron micrographs confirmed the progress of fibril state from globular chains to amyloid. However, the results of ThT fluorescence measurements indicated a concentration-dependent inhibiting effect of chemically synthesized GNPs on insulin fibrillation in vitro, simultaneously by conversion of the formed fibrils into amorphous aggregates. Furthermore, biogenic GNPs were found to more effectively inhibit the fibril formation, compared to chemically synthesized GNPs. Accordingly, just 0.05nmolL -1 of the biogenic GNPs showed similar inhibition property of chemically synthesized GNPs with a concentration of 10nmolL -1 . Both types of GNPs diminished toxicity of insulin fibrils in rat pheochromocytoma PC12 cells viability. Copyright © 2017. Published by Elsevier B.V.

  6. Epidermal growth factor-receptor interaction in rat pheochromocytoma (PC12) and human epidermoid A431 cells: Biochemical and ultrastructural studies

    NARCIS (Netherlands)

    Laat, S.W. de; Boonstra, J.; Mummery, C.L.; Defize, L.; Leunissen, J.; Verkleij, A.J.

    1984-01-01

    Pheochromocytoma cells (clone PC12) have specific plasmamembrane receptors for both epidermal growth factor (EGF) and nerve growth factor (NGF). These growth factors have however, opposite biological effects in PC12 cells; EGF acts mitogenically, while NGF induces differentiation and causes

  7. Adrenocorticotropic Hormone Secreting Pheochromocytoma Underlying Glucocorticoid Induced Pheochromocytoma Crisis

    Directory of Open Access Journals (Sweden)

    Gil A. Geva

    2018-01-01

    Full Text Available Context. Pheochromocytomas are hormone secreting tumors of the medulla of the adrenal glands found in 0.1–0.5% of patients with hypertension. The vast majority of pheochromocytomas secrete catecholamines, but they have been occasionally shown to also secrete interleukins, calcitonin, testosterone, and in rare cases adrenocorticotropic hormone. Pheochromocytoma crisis is a life threatening event in which high levels of catecholamines cause a systemic reaction leading to organ failure. Case Description. A 70-year-old man was admitted with acute myocardial ischemia following glucocorticoid administration as part of an endocrine workup for an adrenal mass. Cardiac catheterization disclosed patent coronary arteries and he was discharged. A year later he returned with similar angina-like chest pain. During hospitalization, he suffered additional events of chest pain, shortness of breath, and palpitations following administration of glucocorticoids as preparation for intravenous contrast administration. Throughout his admission, the patient demonstrated both signs of Cushing’s syndrome and high catecholamine levels. Following stabilization of vital parameters and serum electrolytes, the adrenal mass was resected surgically and was found to harbor an adrenocorticotropic hormone secreting pheochromocytoma. This is the first documented case of adrenocorticotropic hormone secreting pheochromocytoma complicated by glucocorticoid induced pheochromocytoma crisis. Conclusion. Care should be taken when administering high doses of glucocorticoids to patients with suspected pheochromocytoma, even in a patient with concomitant Cushing’s syndrome.

  8. Pheochromocytomas and secreting paragangliomas

    Directory of Open Access Journals (Sweden)

    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.

  9. Pheochromocytomas / Paragangliomas and two cases

    African Journals Online (AJOL)

    Adequate pre- and postoperative medical treatment is important. The history, diagnosis .... of hypertension. Paroxysmal signs and symptoms provide compelling clues for a pheochromocytoma. Stimuli that elicit episodic catecholamine secretion and a paroxysm, even a ... Menopausal syndrome. Cardiovascular. Heart failure.

  10. Stages of Pheochromocytoma and Paraganglioma

    Science.gov (United States)

    ... of the MIBG. Octreotide scan : A type of radionuclide scan used to find certain tumors, including tumors ... cause signs or symptoms are treated with drug therapy. Drug therapy begins when pheochromocytoma or paraganglioma is ...

  11. The president and the pheochromocytoma.

    Science.gov (United States)

    Messerli, Franz H; Loughlin, Kevin R; Messerli, Adrian W; Welch, William R

    2007-05-01

    President Eisenhower experienced an acute heart attack in September 1955 and died of ischemic cardiomyopathy 14 years later. The autopsy revealed, unexpectedly, a 1.5-cm pheochromocytoma in the left adrenal gland. In view of these hitherto unreported findings, the investigators analyzed the blood pressure pattern of the president throughout his life. Although hypertension was documented on and off from 1930 until his death, it is unknown whether the pheochromocytoma was present during his presidency. During the later part of President Eisenhower's life, excessive systolic and diastolic blood pressure spikes were documented, although he concomitantly had severe ischemic cardiomyopathy. In conclusion, most likely, the pheochromocytoma was the underlying cause of this erratic blood pressure pattern and may have worsened the course of the president's ischemic cardiomyopathy.

  12. Hydroxytyrosol increases norepinephrine transporter function in pheochromocytoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Luzon-Toro, Berta [Institute of Parasitology and Biomedicine ' Lopez-Neyra' , Spanish National Research Council (CSIC), 18100 Granada (Spain); Geerlings, Arjan [Puleva Biotech, 18004 Granada (Spain); Hilfiker, Sabine [Institute of Parasitology and Biomedicine ' Lopez-Neyra' , Spanish National Research Council (CSIC), 18100 Granada (Spain)], E-mail: sabine.hilfiker@ipb.csic.es

    2008-10-15

    Introduction: The norepinephrine transporter is responsible for the intracellular uptake of {sup 131}I- iodometaiodobenzylguanidine ({sup 131}I-MIBG), which is used for the diagnostic localization and treatment of pheochromocytomas as well as other tumors such as neuroblastomas and carcinoids. This agent is variably delivered into tumor cells by the norepinephrine transporter, but few studies have shown treatments that work to increase norepinephrine transporter activity. The objective of the present study was to test the possible beneficial effects of hydroxytyrosol in enhancing norepinephrine transporter function, which may have implications for its combined use with {sup 131}I-MIBG in the diagnosis and treatment of pheochromocytomas. Methods: Rat pheochromocytoma PC12 cells were labeled with [{sup 3}H]-norepinephrine in the presence or absence of different concentrations of hydroxytyrosol, a naturally occurring compound with strong antioxidant properties, followed by measurements of uptake and release of radiolabeled norepinephrine. Results: Hydroxytyrosol pronouncedly increased norepinephrine transporter activity, with the rapid onset excluding effects on norepinephrine transporter expression levels. Concomitant with increased norepinephrine transporter activity, hydroxytyrosol caused a decrease of both spontaneous and evoked norepinephrine release, indicating that it affects pre-existing plasma membrane-associated norepinephrine transporter, rather than the incorporation of novel norepinephrine transporter molecules into the plasma membrane. Conclusion: Hydroxytyrosol potently enhances norepinephrine transporter activity in pheochromocytoma PC12 cells, suggesting that combinatorial therapy employing hydroxytyrosol may improve the effectiveness of {sup 131}I-MIBG as a diagnosis and treatment modality.

  13. [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...

  14. Recurrent benign adrenal pheochromocytomas associated with hemihypertrophy.

    Science.gov (United States)

    Pikilidou, Maria; Yavropoulou, Maria; Katsounaros, Marios

    2014-01-01

    We report a case of a female with hemihypertrophy, who developed five recurrences of pheochromocytomas until the age of 35. Timely follow-up of the patient's blood pressure assisted in early diagnosis and treatment of recurrent tumors. Recurrent benign pheochromocytomas should raise suspicion of a genetic syndrome.A pheochromocytoma at a young age has a high propensity to recur and strict follow-up is mandatory.

  15. A retrospective study of pheochromocytoma

    Directory of Open Access Journals (Sweden)

    Larigani B

    1997-08-01

    Full Text Available Pheochromocytoma is a rare disease. A retrospective study of the signs and clinical course of this disorder was performed by evaluating medical records. Our fidings indicate that the prevalence of pheochromocytoma was equal in men and women, and most patients (56% were in their second and third decades of life. In 10% of the cases, the disease was bilateral, and in 13% it was outside the adrenal (totally para-aortic. The tumor was more common on the right side (8%, and 3.5% were familial. Almost all cases had a history of hypertension and hypertensive crises. Attack-like episodes of clinical symptoms and signs and hypertension were observed in 98%, headache in 71% and profuse perspiration in 68% of the cases. An abdominal mass was palapated in 13% of the cases, 26% had overt diabetes, 23% had ECG changes. Malignancy was observed in 4%, with metastases to the liver (n=2 lung (n=1 and spine (n=1. In the latter four cases, the metastic lesion was histologically proven to be pheochromocytoma. In three of the 28 female cases, the first hypertensive crisis occurred during pregnancy causing abortion in one case.

  16. Pelvic Pheochromocytoma Mimicking as Urinary Bladder Pheochromocytoma: Looking Beyond the Obvious

    Directory of Open Access Journals (Sweden)

    Santosh Kumar

    2014-01-01

    Full Text Available Pheochromocytomas located outside the adrenal glands are called paragangliomas. A pelvic location is rare, the most common location for a paraganglioma being the retroperitoneal space. Paragangliomas arise from neural crest cells. Pelvic pheochromocytomas may mimic urinary bladder pheochromocytomas on imaging studies. Patients may present with hypertensive crisis during micturition. We present a 26-year-old female who presented to us with accelerated hypertension with episodes of severe headache and palpitation during micturition. Based on imaging studies, she was diagnosed to have a urinary bladder pheochromocytoma. However, on exploration, the patient was found to have an extravesical pheochromocytoma arising from the left posterolateral pelvic wall, which was excised while preserving the bladder. We present this case report as pelvic pheochromocytomas can mimic bladder pheochromocytomas and are difficult to differentiate on radiological imaging and can lead to inadvertent cystectomy.

  17. Quantitative analysis of the pyrimidine metabolism in pheochromocytoma PC-12 cells

    NARCIS (Netherlands)

    Slingerland, R. J.; van Gennip, A. H.; Bodlaender, J. M.; Voûte, P. A.; van Kuilenburg, A. B.

    1995-01-01

    A detailed quantitative study of pyrimidine metabolism in exponentially growing rat pheochromocytoma PC-12 cells has been performed. The sizes of ribonucleotide pools have been analysed and the pathways and the rates of metabolism of uridine, cytidine and aspartic acid have been determined, based on

  18. Treatment Options for Pheochromocytoma and Paraganglioma

    Science.gov (United States)

    ... of the MIBG. Octreotide scan : A type of radionuclide scan used to find certain tumors, including tumors ... cause signs or symptoms are treated with drug therapy. Drug therapy begins when pheochromocytoma or paraganglioma is ...

  19. General Information about Pheochromocytoma and Paraganglioma

    Science.gov (United States)

    ... of the MIBG. Octreotide scan : A type of radionuclide scan used to find certain tumors, including tumors ... cause signs or symptoms are treated with drug therapy. Drug therapy begins when pheochromocytoma or paraganglioma is ...

  20. Treatment Option Overview (Pheochromocytoma and Paraganglioma)

    Science.gov (United States)

    ... of the MIBG. Octreotide scan : A type of radionuclide scan used to find certain tumors, including tumors ... cause signs or symptoms are treated with drug therapy. Drug therapy begins when pheochromocytoma or paraganglioma is ...

  1. 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

  2. Graves′ disease allied with multiple pheochromocytoma

    Directory of Open Access Journals (Sweden)

    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.

  3. 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)

  4. Pheochromocytoma

    Science.gov (United States)

    ... foods include: Some cheeses Some beers and wines Chocolate Dried or smoked meats Certain medications that can ... multiple organs, particularly tissues of the cardiovascular system, brain and kidneys. Untreated, high blood pressure associated with ...

  5. Somatic RET mutation in a patient with pigmented adrenal pheochromocytoma

    NARCIS (Netherlands)

    Maison, Nicole; Korpershoek, Esther; Eisenhofer, Graeme; Robledo, Mercedes; de Krijger, Ronald; Beuschlein, Felix

    UNLABELLED: Pheochromocytomas (PCC) and paraganglioma (PGL) are rare neuroendocrine tumors arising from chromaffin cells of the neural crest. Mutations in the RET-proto-oncogene are associated with sporadic pheochromocytoma, familial or sporadic medullary thyroid carcinoma (MTC) and multiple

  6. The Pathogenesis of Pheochromocytomas: Of Mice and Men

    NARCIS (Netherlands)

    E. Korpershoek (Esther)

    2011-01-01

    textabstractPheochromocytomas are neuro‐endocrine tumors that arise from the neural crest derived adrenal medullary chromaffin cells, and produce catecholamines. The first description of a patient with pheochromocytomas was done by Fränkel in 1886, but the term pheochromocytoma was invented by

  7. Pheochromocytoma: A Rare Cause of Secondary Hypertension

    Directory of Open Access Journals (Sweden)

    Sahadeb Prasad Dhungana

    2013-06-01

    Full Text Available   Introduction: Pheochromocytoma is a rare tumor, originating from the chromaffin tissue. Its frequency is approximately 1/100,000. The clinical manifestation is due to catecholamine excess, which includes high blood pressure, palpitation, headache, sweating, nausea, vomiting, trembling, weakness, irritation, abdominal and chest pain, dyspnea, red warm face, constipation, polyuria, and polydipsia.   Case Report: We present a case of 53 years old male, hospitalized for hypertensive crisis following the manipulation of left sided frozen shoulder. He had labile blood pressure ranging from 220/120 systolic- 90/60 diastolic, profuse sweating and tachycardia. Findings of Contrast enhanced CT of abdomen was consistent with right adrenal pheochromocytoma and 24 hours urinary VMA was 17 mg /24 hr (Normal <13.6 mg /24hr. After the clinical, paraclinical investigations and radiological tests, it was proved to be a pheochromocytoma. The surgical intervention was planned. But due to unavailability of required antihypertensive drugs in Nepal (alpha-blockers like phentolamine and phenoxybenzamine, surgeons were reluctant to operate, although blood pressure was well controlled with use of sodium nitroprusside during hypertensive crisis and prazosin, a selective alpha blocker as maintainance therapy. The use of prazosin to control hypertension secondary to pheochromocytoma is limited to case report and case series.   Conclusion: Although rare, pheochromocytoma is a treatable surgical cause of secondary hypertension.

  8. Coexistence of pheochromocytoma with uncommon vascular lesions

    Directory of Open Access Journals (Sweden)

    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.

  9. Pheochromocytoma in a white rhinoceros (Ceratotherium simum).

    Science.gov (United States)

    Bertelsen, Mads F; Steele, Shelby L; Grøndahl, Carsten; Baandrup, Ulrik

    2011-09-01

    A 46-yr-old male white rhinoceros (Ceratotherium simum) died during anesthesia following agonal excitation. On postmortem, a well-demarcated 2.5-cm tan mass was identified in the right adrenal gland. Histopathology confirmed the presence of a pheochromocytoma, and elevated levels of epinephrine in serum collected shortly prior to the animal's death, as compared with sera from healthy controls, demonstrated the functional nature of the tumor. Although rare, pheochromocytoma should be considered as a differential diagnosis in cases of suspected hypertension and acute death in rhinos.

  10. Life-Threatening Cardiac Manifestations of Pheochromocytoma

    Directory of Open Access Journals (Sweden)

    Luiz R. Leite

    2010-01-01

    Full Text Available Pheochromocytoma is a catecholamine-secreting tumor of the adrenal glands, usually with benign manifestations, whose typical clinical presentation includes the triad of headache, palpitations and diaphoresis. However, a wide range of signs and symptoms may be present. In the cardiovascular system, the most common signs are labile hypertension and sinus tachycardia. Systolic heart failure and ST-segment deviations mimicking myocardial infarction have also been reported, as well as QT interval prolongation and, rarely, ventricular tachycardia. We describe a challenging diagnosis of pheochromocytoma with many cardiovascular manifestations, which could have been missed due to the absence of typical symptoms.

  11. The Epidemiology of Pheochromocytoma - Is the Incidence Increasing?

    DEFF Research Database (Denmark)

    Ebbehoj, A; Søndergaard, Esben; Trolle, Christian

    Background Though pheochromocytoma is a rare disease, it is a frequent diagnostic dilemma in adrenal incidentaloma individuals necessitating clarification due to the potential life-threatening nature of pheochromocytoma. There is a widespread perception of an increase in the number of patients...... 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...... database. These data will be used to describe the presentation of the disease in the clinic. Incidence rates of pheochromocytoma will be analyzed using Poisson regression, and confidence limits using an approximation to Poisson distribution. Prelimanary Results The process of verifying pheochromocytoma...

  12. 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

  13. Molecular pathology op pheochromocytoma and paraganglioma development

    NARCIS (Netherlands)

    F.H. van Nederveen (Francien)

    2010-01-01

    textabstractPheochromocytomas (PCC) are rare tumours of the adrenal medulla. These tumours are derived from the neural crest, similar to paraganglioma (PGL), which are located in the head and neck region and along the sympathetic chain. Histomorphologically these tumours are identical, although the

  14. 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

  15. 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.

  16. Localization of a pheochromocytoma using I-123 MIBG adrenal scintigraphy.

    Directory of Open Access Journals (Sweden)

    Shirkare S

    1994-04-01

    Full Text Available In a patient with the clinical diagnosis of pheochromocytoma, the localization of the tumor is essential for planning treatment. Recently, we have performed I-123 metaiodobenzylguanidine (MIBG adrenal scintigraphy in a patient presenting with a history of paroxysmal hypertension. Scintigraphy accurately located an ectopic unilateral pheochromocytoma. The scintigraphic diagnosis was confirmed by surgery and a diagnosis of ectopic unilateral pheochromocytoma was made by histopathological examination. This case report illustrates the specific diagnosis of pheochromocytoma by I-123 MIBG scintigraphy which is especially useful when other diagnostic procedures are equivocal.

  17. 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.

  18. Extra-adrenal Pheochromocytoma: Experience in Mulago Hospital ...

    African Journals Online (AJOL)

    ... have a family history of malignancy. Management of extra-adrenal pheochromocytoma is enblock en-mass surgical resection. Chemotherapy, and radiation therapy may be necessary in malignant disease. Longterm follow-up is essential, as extra-adrenal pheochromocytomas can recur many years after initial diagnosis.

  19. Pheochromocytoma presenting as musculoskeletal pain from bone metastases

    Energy Technology Data Exchange (ETDEWEB)

    Lynn, M.D.; Braunstein, E.M.; Shapiro, B.

    1987-10-01

    Six patients presented with musculoskeletal pain resulting from destructive bone lesions. These patients were ultimately shown to have metastatic pheochromocytoma. None of the cases exhibited typical symptoms of metastatic pheochromocytoma, nor was it suspected at the time of presentation. In three patients, hypertension caused pheochromocytoma to be considered as a diagnosis. The three remaining patients, all of whom had documented hypertension in the past, underwent bone biopsy. Two of these patients became markedly hypertensive in the postoperative period. Malignant pheochromocytoma may present with metastatic skeletal disease in some patients in whom the presence of hypertension as well as a carefully elicited history may suggest the diagnosis. In such patients, the possibility of pheochromocytoma should be taken into account, as biopsy may trigger a hypertensive crisis in patients not under adrenergic blockade.

  20. [Pheochromocytoma and pregnancy. A case report].

    Science.gov (United States)

    Merlos-Gutiérrez, Ana Laura; Martínez-García, Manuel; Pérez-Martínez, Andrés; Chávez-Martínez, Sareni; Sereno-Coló, José Antonio

    2015-11-01

    Pheochromocytoma is a tumor originating in the chromaffin cells. These tumors secrete catecholamines which act on target organs and cause hypertensive crises. They are rare during pregnancy, and a differential diagnosis must be carried out mainly with pregnancy-induced hypertension. A 22-year-old patient in week 11.5 of pregnancy presented at the Hospital General Dr. Miguel Silva in Morelia, Michoacán with hypertension that had existed for more than two years with poor adherence to treatment. At the time of referral to our unit she presented a hypertensive crisis that had been unresponsive to all antihypertensive treatments. Following the establishment of a study protocol, a diagnosis of posterior left adrenal pheochromocytoma was made. After subsequent pharmacological treatment with alpha and beta blockers, a left adrenalectomy was performed. The patient did not require antihypertensive treatment following surgery. The histopathological report indicates the presence of a nodular and vascularized left adrenal gland weighing 25 g and measuring 5 x 4 x 3.5 cm. Gland consistency was soft, and the presence of cystic lesions in parenchymal tissue was noted. A yellowish-brown color and sponge-like appearance were also present. Such features support a diagnosis of pheochromocytoma. The pregnancy continued normally until week 32, when the patient presented to our department with active-phase preterm labor. A Cesarean section was performed with the delivery of a live female weighing 1400 gr. The infant is currently alive and well. Thus, it is important that obstetrician knows this disease and its management during pregnancy; so we present this case report.

  1. Pheochromocytoma Masquerading as “Diabetic Ketoacidosis”

    Directory of Open Access Journals (Sweden)

    Jeffrey Stephen Hedley MD

    2016-04-01

    Full Text Available Diabetic ketoacidosis is a routinely encountered diagnosis in medicine. Physicians are trained early on to look for precipitants. Most clinicians assess for medication compliance, infection, ischemia, and the like. We present a case of pheochromocytoma presenting as “diabetic ketoacidosis.” The case serves as an example for broadening the differential diagnosis for patients with similar presentations. Additionally, the case helps inform our understanding of the so-called “stress reactions” that are commonly invoked in clinical rationale.

  2. Translation of tyrosine hydroxylase from poly(A)-mRNA in pheochromocytoma cells is enhanced by dexamethasone.

    OpenAIRE

    Baetge, E E; Kaplan, B B; Reis, D J; Joh, T H

    1981-01-01

    Polysomal poly(A)-mRNA was purified from a clonal cell line of rat pheochromocytoma (PC 12) and translated in a reticulocyte cell-free protein-synthesizing system. Tyrosine hydroxylase [tyrosine 3-monooxygenase; L-tyrosine, tetrahyropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] was isolated from other protein by immunoprecipitation and NaDodSO4/polyacrylamide gel electrophoresis. The molecular weight and relative proportion of tyrosine hydroxylase to other proteins synthesi...

  3. Spontaneous adrenal pheochromocytoma rupture complicated by intraperitoneal hemorrhage and shock

    Directory of Open Access Journals (Sweden)

    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.

  4. Low sensitivity of glucagon provocative testing for diagnosis of pheochromocytoma.

    Science.gov (United States)

    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.

  5. Integrative analysis of neuroblastoma and pheochromocytoma genomics data

    Directory of Open Access Journals (Sweden)

    Szabó Peter M

    2012-10-01

    Full Text Available Abstract Background Pheochromocytoma and neuroblastoma are the most common neural crest-derived tumors in adults and children, respectively. We have performed a large-scale in silico analysis of altogether 1784 neuroblastoma and 531 pheochromocytoma samples to establish similarities and differences using analysis of mRNA and microRNA expression, chromosome aberrations and a novel bioinformatics analysis based on cooperative game theory. Methods Datasets obtained from Gene Expression Omnibus and ArrayExpress have been subjected to a complex bioinformatics analysis using GeneSpring, Gene Set Enrichment Analysis, Ingenuity Pathway Analysis and own software. Results Comparison of neuroblastoma and pheochromocytoma with other tumors revealed the overexpression of genes involved in development of noradrenergic cells. Among these, the significance of paired-like homeobox 2b in pheochromocytoma has not been reported previously. The analysis of similar expression patterns in neuroblastoma and pheochromocytoma revealed the same anti-apoptotic strategies in these tumors. Cancer regulation by stathmin turned out to be the major difference between pheochromocytoma and neuroblastoma. Underexpression of genes involved in neuronal cell-cell interactions was observed in unfavorable neuroblastoma. By the comparison of hypoxia- and Ras-associated pheochromocytoma, we have found that enhanced insulin like growth factor 1 signaling may be responsible for the activation of Src homology 2 domain containing transforming protein 1, the main co-factor of RET. Hypoxia induced factor 1α and vascular endothelial growth factor signaling included the most prominent gene expression changes between von Hippel-Lindau- and multiple endocrine neoplasia type 2A-associated pheochromocytoma. Conclusions These pathways include previously undescribed pathomechanisms of neuroblastoma and pheochromocytoma and associated gene products may serve as diagnostic markers and therapeutic

  6. 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

    2017-09-25

    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.

  7. 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

  8. Congenital hemihypertrophy and pheochromocytoma, not a coincidental combination?

    Science.gov (United States)

    van den Akker, Erica L T; de Krijger, Ronald R; de Herder, Wouter W; Drop, Stenvert L S

    2002-03-01

    We describe a 19-year-old female, known to have congenital hemihypertrophy, who presented with bilateral benign pheochromocytoma. This is the second time that this combination has been reported in the literature. We speculate that the combination of congenital hemihypertrophy and pheochromocytoma is not coincidental and could be part of the clinical spectrum of the Beckwith-Wiedemann syndrome. in patients with congenital hemihypertrophy, the physician should be aware of the symptoms of pheochromocytoma. Besides screening for abdominal tumours, analysis of plasma and/or urinary catecholamines and/or their metabolites should be considered.

  9. 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.

  10. Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma.

    Science.gov (United States)

    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; Pacak, Karel; Nathanson, Katherine L; Wilkerson, Matthew D

    2017-02-13

    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 PCC/PGL susceptibility genes. We identified CSDE1 as a somatically mutated driver gene, complementing four known drivers (HRAS, RET, EPAS1, and NF1). We also discovered fusion genes in PCCs/PGLs, involving MAML3, BRAF, NGFR, and NF1. Integrated analysis classified PCCs/PGLs into four molecularly defined groups: a kinase signaling subtype, a pseudohypoxia subtype, a Wnt-altered subtype, driven by MAML3 and CSDE1, and a cortical admixture subtype. Correlates of metastatic PCCs/PGLs included the MAML3 fusion gene. This integrated molecular characterization provides a comprehensive foundation for developing PCC/PGL precision medicine. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Pseudocystic pheochromocytoma associated with pneumatosis cystoides intestinalis

    Energy Technology Data Exchange (ETDEWEB)

    Alanen, A.; Kormano, M.

    1982-02-01

    The authors report a case of a large pseudocystic pheochromocytoma, which initially was operated on and histologically diagnosed as a pancreatic pseudocyst. After recurrence, a multilocular cystic tumor was found both by ultrasonography and CT. ERCP demonstrated a cut-off of the pancreatic duct. Re-operation revealed a cystic adrenal tumor anastomosed to the stomach. The operation was complicated by a hypertensive crisis and a subsequent subendocardial infarction. In the preoperative period the patient had continuous diarrhea and pneumatosis cystoides intestinalis was demonstrated by double contrast barium enema. The pneumatosis disappeared within three months but a recurrent tumor appeared. The importance of CT in the preoperative work-up of upper abdominal lesions is emphasized, as atypical cystic masses may cause differential diagnostic problems in surgery or even in localized biopsies, while CT would give a better overall view of the tumor.

  12. Brief communication: radiographic contrast infusion and catecholamine release in patients with pheochromocytoma.

    NARCIS (Netherlands)

    Baid, S.K.; Lai, E.W.; Wesley, R.A.; Ling, A.; Timmers, H.J.L.M.; Adams, K.T.; Kozupa, A.; Pacak, K.

    2009-01-01

    BACKGROUND: Contrast-enhanced computed tomography (CT) is useful for localizing pheochromocytoma. However, in patients with suspected pheochromocytoma, CT is often canceled or not performed because of the strong belief that intravenous contrast may induce hypertensive crisis. OBJECTIVE: To examine

  13. Introduction of a Case of Bilateral Pheochromocytoma Tumor

    Directory of Open Access Journals (Sweden)

    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

  14. Marker-Negative Pheochromocytoma Associated with Inferior Vena Cava Thrombosis

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  16. Targeting heat shock protein 90 for the treatment of malignant pheochromocytoma.

    Directory of Open Access Journals (Sweden)

    Alessio Giubellino

    Full Text Available Metastatic pheochromocytoma represents one of the major clinical challenges in the field of neuroendocrine oncology. Recent molecular characterization of pheochromocytoma suggests new treatment options with targeted therapies. In this study we investigated the 90 kDa heat shock protein (Hsp90 as a potential therapeutic target for advanced pheochromocytoma. Both the first generation, natural product Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG, tanespimycin, and the second-generation synthetic Hsp90 inhibitor STA-9090 (ganetespib demonstrated potent inhibition of proliferation and migration of pheochromocytoma cell lines and induced degradation of key Hsp90 clients. Furthermore, ganetespib induced dose-dependent cytotoxicity in primary pheochromocytoma cells. Using metastatic models of pheochromocytoma, we demonstrate the efficacy of 17-AAG and ganetespib in reducing metastatic burden and increasing survival. Levels of Hsp70 in plasma from the xenograft studies served as a proximal biomarker of drug treatment. Our study suggests that targeting Hsp90 may benefit patients with advanced pheochromocytoma.

  17. Biochemical diagnosis of pheochromocytoma: which test is best?

    NARCIS (Netherlands)

    Lenders, J.W.M.; Pacak, K.; Walther, M.M.; Linehan, W.M.; Mannelli, M.; Friberg, P.; Keiser, H.R.; Goldstein, D.S.; Eisenhofer, G.

    2002-01-01

    CONTEXT: Diagnosis of pheochromocytoma depends on biochemical evidence of catecholamine production by the tumor. However, the best test to establish the diagnosis has not been determined. OBJECTIVE: To determine the biochemical test or combination of tests that provides the best method for diagnosis

  18. Update on Modern Management of Pheochromocytoma and Paraganglioma

    NARCIS (Netherlands)

    Lenders, J.W.M.; Eisenhofer, G.

    2017-01-01

    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

  19. Management of pheochromocytoma: Old ideas and new drugs ...

    African Journals Online (AJOL)

    Pheochromocytoma presents a challenge to the surgery team because of its clinical features and implications. The patient must be treated before the surgery until a stable hemodynamically state is achieved. The preoperative treatment includes α2‑short acting adrenergic blocking and β‑blocker agents. The most crucial ...

  20. Pheochromocytoma : a review on preoperative treatment with phenoxybenzamine or doxazosin

    NARCIS (Netherlands)

    van der Zee, P A; de Boer, A|info:eu-repo/dai/nl/075097346

    2014-01-01

    BACKGROUND: During surgical treatment of pheochromocytoma,`haemodynamic instability may occur. To prevent this, patients receive preoperative treatment with an alpha-blocker. Nowadays, some centres use phenoxybenzamine, while others use doxazosin. The purpose of this review is to analyse the current

  1. Risk factors for hypertensive attack during pheochromocytoma resection

    Directory of Open Access Journals (Sweden)

    Se Yun Kwon

    2016-05-01

    Full Text Available Purpose: We aimed to retrospectively evaluate the risk factors for hypertensive attack during adrenalectomy in patients with pheochromocytoma. Despite the development of newer surgical and anesthetic techniques for the management of pheochromocytoma, intraoperative hypertensive attack continues to present a challenge. Materials and Methods: Data from 53 patients diagnosed with pheochromocytoma at Kyungpook National Uriversity Medical Center between January 2000 and June 2012 were retrospectively analyzed. The subjects were divided into 2 groups depending on the presence or absence of hypertensive attack at the time of surgery. Patient demographic characteristics and preoperative evaluations were assessed for their prognostic relevance with respect to hypertensive attack. A univariate analysis was conducted, and a multivariate logistic regression analysis was also performed. Results: In the univariate analysis, systolic blood pressure at presentation, preoperative hormonal status (including epinephrine, norepinephrine, vanillylmandelic acid, and metanephrine levels in a 24-hour urine sample, tumor size, and postoperative systolic blood pressure were significantly associated with the development of hypertensive attack. In the multivariate analysis, preoperative epinephrine level and tumor size were independent factors that predicted hypertensive attack. The highest odds ratio for tumor size (2.169 was obtained at a cutoff value of 4.25 cm and the highest odds ratio for preoperative epinephrine (1.020 was obtained at a cutoff value of 166.3 μg/d. Conclusions: In this study, a large tumor size and an elevated preoperative urinary epinephrine level were risk factors for intraoperative hypertensive attack in patients with pheochromocytoma.

  2. 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

  3. Bilateral pheochromocytomas in a child who had hemihypertrophy and alteration in the VHL gene.

    Science.gov (United States)

    Amini, Zarlasht; Babovic-Vuksanovic, Dusica; Lteif, Aida

    2013-01-01

    The association of hypertrophy with neoplasm is well-known. Pheochromocytoma is a rare neoplasm in children. Isolated hemihypertrophy and hemihypertrophy linked to other genetic disorders have rarely been associated with the development of pheochromocytoma, with only two cases reported to date. We report a novel case of a 4-year-old male with bilateral adrenal pheochromocytomas and lower extremity hemihypertrophy in the setting of von Hippel-Lindau syndrome.

  4. Optimizing Hemodynamics with Transcatheter Arterial Embolization in Adrenal Pheochromocytoma Rupture: A Case Report.

    Science.gov (United States)

    Edo, Naoki; Yamamoto, Takahiro; Takahashi, Satoshi; Mashimo, Yamato; Morita, Koji; Saito, Koji; Kondo, Hiroshi; Sasajima, Yuko; Kondo, Fukuo; Okinaga, Hiroko; Tsukamoto, Kazuhisa; Ishikawa, Toshio

    2018-02-28

    Pheochromocytoma rupture is rare, and emergent adrenalectomy is associated with a high mortality. We herein report a patient with pheochromocytoma rupture who was stabilized by transcatheter arterial embolization (TAE) and subsequently underwent elective surgery. A 45-year-old man presented with the sudden onset of left lateral abdominal pain, headache, chest discomfort, high blood pressure, and adrenal hemorrhaging on enhanced abdominal computed tomography. TAE was performed under a provisional diagnosis of pheochromocytoma rupture. Following oral doxazosin, he underwent elective left adrenalectomy four and a half months after TAE. Stabilizing the hemodynamic status by TAE before adrenalectomy is a viable option for treating pheochromocytoma rupture.

  5. 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.

  6. Pheochromocytoma: State of the Art and Guide to Evaluation and Management

    Directory of Open Access Journals (Sweden)

    Pradeep PV

    2016-04-01

    Full Text Available Pheochromocytoma is so called because it acquires a dusky color on staining with chromium salts. Roux in Switzerland and Charles Mayo in United States first performed excision of Pheochromocytoma. The excess circulating catecholamines have action on the adrenergic receptors. Approximately 0.5% of hypertensives are having pheochromocytoma of which 10% are accidentally detected. 85% of pheochromocytoma occur in adrenal medulla, 8% in the organ of Zuckerkandl. Ectopic sites are rarely involved like the chest (2%, neck (1% and urinary bladder.

  7. Multiple gastrointestinal stromal tumors and bilateral pheochromocytoma in neurofibromatosis

    Science.gov (United States)

    Kramer, Klaus; Hasel, Cornelia; Aschoff, Andrik J; Henne-Bruns, Doris; Wuerl, Peter

    2007-01-01

    The coincidence of a gastrointestinal stromal tumor (GIST) and a neuroendocrine tumor (NET) in neurofibromatosis type 1 (NF1) is described only five times within the literature. We report on a 63 year old Caucasian female with the rare condition of neurofibromatosis type 1 coinciding with recurrent gastrointestinal stromal tumor plus bilateral pheochromocytoma (PCC). After a history of palpitations and dizziness that lasted for years, a left adrenal mass was detected by CT. Laparotomy revealed a pheochromocytoma of the left adrenal gland while an ileoterminal GIST was found incidentally intraoperatively. After six months contralateral PCC and multiple recurrent GIST were resected again. After four years the patient is doing well without any signs of further recurrent tumors. Discussion includes review of the literature. PMID:17659681

  8. Pheochromocytoma of the urinary bladder - a case report

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

  10. Pheochromocytoma: clinical review based on a rare case in adolescence.

    Science.gov (United States)

    Alface, Marisa Maibel; Moniz, Patricia; Jesus, Susana; Fonseca, Cândida

    2015-08-04

    Pheochromocytomas are rare tumours originating in chromaffin cells, representing 0.1-1% of all secondary hypertension (HT) cases. The majority are benign and unilateral, characterised by the production of catecholamines and other neuropeptides. Mainly located in the adrenal gland, they are more frequent between the 3rd and 5th decades of life; however, 10-25% can be associated with genetic familial syndromes (multiple endocrine neoplasia type 2 (MEN 2), type 1 neurofibromatosis and Von-Hippel-Landau disease in younger ages. The authors present a rare case of secondary HT due to a pheochromocytoma in a 15-year-old patient, whose metanephrine assay confirmed the diagnosis, and abdominal ultrasound and CT localised the tumour in the adrenal gland. HT was controlled with α and β blockers, with posterior retroperitoneal laparoscopic surgical intervention and subsequent resolution of HT. Age and concomitant hyperparathyroidism compelled genetic testing for the exclusion of MEN 2, which was negative. 2015 BMJ Publishing Group Ltd.

  11. Mutations in the RET proto-oncogene in sporadic pheochromocytomas

    Energy Technology Data Exchange (ETDEWEB)

    Thibodeau, S.N.; Lindor, N.M.; Honchel, R. [Mayo Clinic and Foundation, Rochester, MN (United States)] [and others

    1994-09-01

    Mutations in the RET proto-oncogene have recently been demonstrated in kindreds with Multiple Endocrine Neoplasia (MEN) types 2A and 2B. Both of these autosomal dominant disorders are characterized by the development of neoplasia in cell lines of neural crest origin, such as medullary throid carcinomas and pheochromocytomas. Individuals with MEN 2B have, in addition, ganglioneuromas of the lips, tongue and colon, a marfanoid habitus, and corneal nerve thickening. Approximately 90% of patients with MEN 2A have a germline mutation in exons 10 or 11, while 95% of patients with MEN 2B have a T{yields}C transition in codon 918 of exon 16. In this study, pheochromocytomas from 29 individuals who had no clinical evidence of MEN 2A or 2B (sporadic) were examined for the presence of either germline or somatic mutations in exons 10, 11, and 16 of the RET proto-oncogene. Of the 29 tumors examined, 3 (10%) were found to have a mutation in one of the three exons. One tumor had a G{yields}A transition in codon 609 (exon 10), another had a 6 bp deletion encompassing codons 632 & 633 (exon 11), and the final tumor had a T{yields}C transition in codon 918 (exon 16). These mutations were not found in the corresponding normal DNA from these individuals, indicating that the mutation were somatic in origin. Although we cannot exclude the possibility of mutations in other regions of the RET proto-oncogene, our data suggests that: (1) individuals presenting with apparently sporadic pheochromocytomas are not likely to have undiagnosed MEN 2A or 2B; and (2) somatic mutations in the RET proto-oncogene contribute to the process of tumorigenesis in a small percentage of sporadic pheochromocytomas.

  12. Molecular imaging and theranostic approaches in pheochromocytoma and paraganglioma.

    Science.gov (United States)

    Taïeb, David; Pacak, Karel

    2018-02-15

    Pheochromocytomas and their extra-adrenal counterpart paragangliomas (PGLs; together called PPGLs), belong to the family of neural crest-derived tumors. Given the overexpression of a wide variety of specific targets in PPGLs, it seems that these tumors are optimally suited to be imaged by specific radiopharmaceuticals. Thus, theranostics approaches with somatostatin agonists and antagonists are rapidly evolving in the setting of these tumors and may be considered as the next step in the therapeutic arsenal of metastatic PPGLs.

  13. Pheochromocytoma presenting as recurrent urinary tract infections : a case report

    Directory of Open Access Journals (Sweden)

    MEntee Gerard P

    2011-01-01

    Full Text Available Abstract Introduction Pheochromocytomas are rare, potentially fatal, neuroendocrine tumors of the adrenal medulla or extra-adrenal paraganglia. Their clinical presentation varies greatly from the classic triad of episodic headache, diaphoresis and tachycardia to include a spectrum of non-specific symptomatology. Case presentation A 43-year-old Caucasian woman was referred to us from primary care services with a three-month history of recurrent urinary tract infections on a background of hypertension, latent autoimmune diabetes of adulthood and autoimmune hypothyroidism. At 38 years she required insulin therapy. Despite medication compliance and dietary control, she reported a recent history of increased insulin requirements and uncontrolled hypertension with concomitant recurrent urinary tract infections. A renal ultrasound examination, to rule out underlying renal pathology, revealed an incidental 8cm right adrenal mass of both solid and cystic components. A subsequent computed tomography of her abdomen and pelvis confirmed a solid heterogeneous mass consistent with a pheochromocytoma. There were no other features suggestive of multiple endocrine neoplasia. Urinary collection over 24 hours revealed grossly elevated levels of catecholamines and metabolites. Following an open right adrenalectomy, our patient's insulin requirements were significantly reduced and her symptoms resolved. Two weeks post-operatively, an iodine-131-metaiodobenzylguanidine scintigraphy was negative for residual tumor and metastatic disease. Urinary catecholamine and metabolite concentrations were within the normal range at a follow-up six months later. Conclusion Pheochromocytoma is a rare catecholamine-producing tumor requiring a high index of suspicion for early diagnosis. Our case report serves to highlight the importance of considering pheochromocytoma as a differential diagnosis in the atypical setting of recurrent urinary tract infections and concomitant autoimmune

  14. Unexpected Small Urinary Bladder Pheochromocytoma: A Nonspecific Presentation

    Directory of Open Access Journals (Sweden)

    Faouzi Mallat

    2013-01-01

    Full Text Available Objectives. Pheochromocytoma of the urinary bladder is an extremely rare tumor that typically presents with a hypertensive crisis during micturition. Preoperatively, it may be misdiagnosed due to nonspecific symptomatology, physical, and radiologic findings. Method. We report a case of unsuspected small pheochromocytoma which was incidentally found by CT scan and confirmed by the histological aspects after transurethral resection in a 63-year-old woman. Here, we have described the clinical presentation, physical findings, laboratory investigations, and treatment provided in our case. We have also included radiological images and histopathology slides with input from both radiologists and pathologists. Surgical management and postoperative follow-up are discussed, as are details of previous published data. Results. After undergoing surgical treatment (transurethral resection, our patient is asymptomatic, with complete resolution of her pathology. Conclusion. Diagnosis is difficult before histopathological examination and should be considered in patients with no risk factors for usual bladder tumor. Our purpose is to raise clinician's awareness for this condition so that they will be more likely to diagnose it. This will facilitate prompt diagnosis and treatment and especially prevent complications due to pheochromocytoma which may be severe.

  15. Pheochromocytoma cell lines from heterozygous neurofibromatosis knockout mice.

    Science.gov (United States)

    Powers, J F; Evinger, M J; Tsokas, P; Bedri, S; Alroy, J; Shahsavari, M; Tischler, A S

    2000-12-01

    Transplantable tumors and cell lines have been developed from pheochromocytomas arising in mice with a heterozygous knockout mutation of the neurofibromatosis gene, Nf1. Nf1 encodes a ras-GTPase-activating protein, neurofibromin, and mouse pheochromocytoma (MPC) cells in primary cultures typically show extensive spontaneous neuronal differentiation that may result from the loss of the remaining wild-type allele and defective regulation of ras signaling. However, all MPC cell lines express neurofibromin, suggesting that preservation of the wild-type allele may be required to permit the propagation of MPC cells in vitro. MPC lines differ from PC12 cells in that they express both endogenous phenylethanolamine N-methyltransferase (PNMT) and full-length PNMT reporter constructs. PNMT expression is increased by dexamethasone and by cell-cell contact in suspension cultures. Mouse pheochromocytomas are a new tool for studying genes and signaling pathways that regulate cell growth and differentiation in adrenal medullary neoplasms and are a unique model for studying the regulation of PNMT expression.

  16. Acute aortic dissection in patient with suspected pheochromocytoma

    Directory of Open Access Journals (Sweden)

    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.

  17. 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

  18. The usefulness of I-131 MIBG scintigraphy in extra-adrenal lesions of pheochromocytoma

    International Nuclear Information System (INIS)

    Kubo, Atsushi; Nakayama, Toshitake; Nishiguchi, Iku; Hashimoto, Teisuke; Kunieda, Etsuo; Hashimoto, Shozo

    1988-01-01

    I-131 metaiodobenzylguanidine (MIBG) scintigraphy has been performed in 55 patients with suspected pheochromocytomas, from January, 1984. I-131 MIBG scintigraphy was performed after 0.5 mCi was injected intravenously over 20 to 30 seconds. Whole body image and/or spot images of head, chest, posterior midabdomen and lower anterior abdomen were obtained 4, 24, 48 and occasionally 72 hours later by means of Toshiba GCA-90 B gamma camera with a high-energy, parallelhole collimator interfaced to a data processor. Thyroid uptake of I-131 was blocked by Lugol solution several drops per day, beginning two days before the tracer injection. 13 extra-adrenal lesions of 3 matastatic pheochromocytomas and 2 extra-adrenal pheochromocytomas could be detected by I-131 MIBG scintigraphy. Extensive bone, liver, lung and lymph nodes metastases were demonstrated by I-131 MIBG scintigraphy in 3 patients with metastatic pheochromocytomas. In 1 of 2 patients with extra-adrenal pheochromocytoma, an abnormal concentration of I-131 MIBG was observed in anterior middle mediastinum proved to be mediastinal ectopic pheochromocytoma, and in another patient it was seen in the region of visceral paraganglia, while X-ray CT failed to demonstrate the tumors in both patients. Thus I-131 MIBG scintigraphy has proved to be safe, specific and noninvasive, and it has been of considerable value, especially in the location of extra-adrenal pheochromocytoma and metastatic pheochromocytoma. (author)

  19. Novel Preclinical Testing Strategies for Treatment of Metastatic Pheochromocytoma

    Science.gov (United States)

    2015-11-01

    mitochondrial proteins comprising other ETC Complexes (I, IV, III and V) were minimally affected (Fig. 3a). Immune complexes precipitated from...of Complex II (30 kDa), core 2 of Complex III (B50 kDa) and F1a (ATP synthase) of Complex V (B60 kDa) was used. The complete chemical synthesis, HPLC...pheochromocytoma have not clearly shown any ther- apeutic benefit. The mTOR inhibitor everolimus (RAD001; Novartis, Basel , Switzerland) failed to demonstrate a

  20. Persistent Hiccups—An Unusual Presentation of Bilateral Pheochromocytoma without Syndromic Association: A Case Report

    Directory of Open Access Journals (Sweden)

    Nitin Aherrao

    2012-01-01

    Full Text Available Pheochromocytoma is a rare catecholamine-producing tumor arising from chromaffin tissue in the adrenal medulla, occurring in less than 0.2 percent of patients with hypertension. The mean age at diagnosis is about 40 years. Pheochromocytomas are commonly inherited as features of multiple endocrine neoplasia type 2 or several other pheochromocytoma-associated syndromes and have variable clinical presentation. Among the presenting symptoms, episodes of palpitations, headaches, and profuse sweating are typical and constitute a classic triad. We report a case of a 17-year-old male patient with rare bilateral pheochromocytoma presenting with persistent hiccups for 4 months and blurring of vision for 1 week, later followed by hypertensive crisis. There was neither family history of pheochromocytoma nor any classic symptoms. Patient was diagnosed with bilateral pheochromocytoma without any syndromic association. But still this patient needs to be followed for future development of medullary carcinoma of thyroid because it could be an initial presentation of MEN 2A/2B/VHL syndromes. Our paper highlights the importance of maintaining a high level of suspicion for persistent hiccups and careful clinical screening for hypertension even in absence of associated syndromes of pheochromocytoma and classical symptoms to achieve prompt diagnosis and to avoid improper management.

  1. Mutation analysis of the RET gene in individuals with sporadic and familial pheochromocytoma

    Energy Technology Data Exchange (ETDEWEB)

    Iyengar, S.; Sirugo, G.; Bale, A.E. [Yale Univ. School of Medicine, New Haven, CT (United States)] [and others

    1994-09-01

    Pheochromocytoma is common to many familial cancer syndromes including multiple endocrine neoplasia type 2A (MEN2A), von Hippel-Lindau (VHL) and neurofibromatosis (NF). Although sporadic cases of pheochromocytoma have been examined for mutations in exons 10, 11 and 16 of the RET gene, only one case with a mutation in exon 16 has been reported thus far. We are performing systematic examination of exons of the RET gene, which has previously been associated with mutation in both MEN2 A and B, to determine the role RET may play in the etiology of pheochromocytoma. Seventeen cases of sporadic pheochromocytoma and 3 cases of sporadic medullary thyroid carcinoma were obtained from the pathology archives. Histopathology of all specimens was confirmed to be either pheochromocytoma or medullary thyroid carcinoma before DNA was extracted from 0.5{mu} thin sections of paraffin-embedded tissue. DNA from familial pheochromocytoma patients was also available for analysis. All sporadic and familial cases were amplified for exons 2, 6 and 16 of the RET gene. Single strand conformational polymorphism (SSCP) analysis was performed for exons 2 and 6. On finding a variation in the SSCP pattern in the pheochromocytoma kindred we sequenced all the samples for exon 2. A single base pair variation was found, which did not segregate with pheochromocytoma in the family. No variant SSCP patterns have been observed with the exon 6 PCR products thus far. Exon 16 PCR products were subjected to DNA restriction analysis with Fok I. This enzyme detects a single base pair change associated with MEN2 B. With the exception of one sample with sporadic medullary thyroid carcinoma, all samples showed the normal pattern on DNA restriction analysis. Thus we can exclude exons 2 and 6 of the RET gene in the pathogenesis of pheochromocytoma. SSCP analyses with other exons in the RET gene are underway.

  2. Pheochromocytoma with Markedly Abnormal Liver Function Tests and Severe Leukocytosis

    Directory of Open Access Journals (Sweden)

    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.

  3. 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.

  4. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  6. Perirenal (18)F-FDG Uptake in a Patient with a Pheochromocytoma.

    Science.gov (United States)

    Park, Jihyun; Byun, Byung Hyun; Jung, Chang Won; Moon, Hansol; Chang, Kyoung Jin; Lim, Ilhan; Kim, Byung Il; Choi, Chang Woon; Lim, Sang Moo

    2014-09-01

    Increased (18)F-fluorodeoxyglucose (FDG) uptake of brown fat on (18)F-FDG positron emission tomography (PET) originating from physiological activation is a common incidental finding and is usually located in the neck, shoulder, and supraclavicular areas. We present a case of an incidental pheochromocytoma showing diffusely increased (18)F-FDG uptake in bilateral perirenal fat tissue as well as supraclavicular and paravertebral fat tissue on (18)F-FDG PET/CT. The patient had no clinical symptoms except hypertension, and a pheochromocytoma was confirmed in a postsurgical specimen. A pheochromocytoma should be considered a cause in cases of increased (18)F-FDG uptake of perirenal brown fat.

  7. Exome sequencing identifies MAX mutations as a cause of hereditary pheochromocytoma.

    Science.gov (United States)

    Comino-Méndez, Iñaki; Gracia-Aznárez, Francisco J; Schiavi, Francesca; Landa, Iñigo; Leandro-García, Luis J; Letón, Rocío; Honrado, Emiliano; Ramos-Medina, Rocío; Caronia, Daniela; Pita, Guillermo; Gómez-Graña, Alvaro; de Cubas, Aguirre A; Inglada-Pérez, Lucía; Maliszewska, Agnieszka; Taschin, Elisa; Bobisse, Sara; Pica, Giuseppe; Loli, Paola; Hernández-Lavado, Rafael; Díaz, José A; Gómez-Morales, Mercedes; González-Neira, Anna; Roncador, Giovanna; Rodríguez-Antona, Cristina; Benítez, Javier; Mannelli, Massimo; Opocher, Giuseppe; Robledo, Mercedes; Cascón, Alberto

    2011-06-19

    Hereditary pheochromocytoma (PCC) is often caused by germline mutations in one of nine susceptibility genes described to date, but there are familial cases without mutations in these known genes. We sequenced the exomes of three unrelated individuals with hereditary PCC (cases) and identified mutations in MAX, the MYC associated factor X gene. Absence of MAX protein in the tumors and loss of heterozygosity caused by uniparental disomy supported the involvement of MAX alterations in the disease. A follow-up study of a selected series of 59 cases with PCC identified five additional MAX mutations and suggested an association with malignant outcome and preferential paternal transmission of MAX mutations. The involvement of the MYC-MAX-MXD1 network in the development and progression of neural crest cell tumors is further supported by the lack of functional MAX in rat PCC (PC12) cells and by the amplification of MYCN in neuroblastoma and suggests that loss of MAX function is correlated with metastatic potential.

  8. DIFFERENTIAL MODULATION OF CATECHOLAMINES BY CHLOROTRIAZINE HERBICIDES IN PHEOCHROMOCYTOMA (PC12) CELLS IN VITRO

    Science.gov (United States)

    Differential modulation of catecholamines by chlorotriazine herbicides in pheochromocytoma (PC12) cells in vitro.Das PC, McElroy WK, Cooper RL.Curriculum in Toxicology, University of North Carolina, Chapel Hill 27599, USA.Epidemiological, wildlife, and lab...

  9. [(123)I]metaiodobenzylguanidine and [(111)In]octreotide uptake in begnign and malignant pheochromocytomas

    NARCIS (Netherlands)

    E. van der Harst (Erwin); E.P. Krenning (Eric); D.J. Kwekkeboom (Dirk Jan); F.T.B. Bosman (Fré); H.A. Bruining (Hajo); H.J. Bonjer (Jaap); S.W.J. Lamberts (Steven); F. Boomsma (Frans); Th. Stijnen (Theo); W.W. de Herder (Wouter); R.R. de Krijger (Ronald); A.H. van den Meiracker (Anton)

    2001-01-01

    textabstractSelecting the appropriate approach for resection and follow-up of pheochromocytomas (PCCs) is highly dependent upon reliable localization and exclusion of multifocal, bilateral, or metastatic disease. Metaiodobenzylguanidine (MIBG) scintigraphy was

  10. Risk of catecholamine crisis in patients undergoing resection of unsuspected pheochromocytoma

    Directory of Open Access Journals (Sweden)

    Gina Song

    2011-02-01

    Full Text Available PURPOSE: To report the risk of catecholamine crisis in patients undergoing resection of unsuspected pheochromocytoma. MATERIALS AND METHODS: Over a four-year period, we retrospectively identified four patients who underwent resection of adrenal pheochromocytoma in whom the diagnosis was unsuspected based on preoperative clinical, biochemical, and imaging evaluation. RESULTS: None of the patients exhibited preoperative clinical features of catecholamine excess. Preoperative biochemical screening in two patients was normal. CT scan performed in all patients demonstrated a nonspecific enhancing adrenal mass. During surgical resection of the adrenal mass, hemodynamic instability was observed in two of four patients, and one of these two patients also suffered a myocardial infarct. CONCLUSION: Both surgeons and radiologists should maintain a high index of suspicion for pheochromocytoma, as the tumor can be asymptomatic, biochemically negative, and have nonspecific imaging features. Resection of such unsuspected pheochromocytomas carries a substantial risk of intraoperative hemodynamic instability.

  11. Familial pheochromocytoma associated with a novel mutation in the von Hippel-Lindau gene

    Energy Technology Data Exchange (ETDEWEB)

    Gross, D.J.; Avishai, N.; Meiner, V.; Abeliovich, D.; Filon, D. [Hadassah Univ. Hospital and the Hebrew Univ.-Hadassah Medical School, Jerusalem (Israel)] [and others

    1996-01-01

    We report a three generation, 25 member kindred with familial pheochromocytoma. Seven subjects of generations I and II had pheochromocytoma, in five of the seven, the tumors were bilateral, and in two of the seven, the tumors were both adrenal and extraadrenal. One patient also had a carotid body chemodectoma, and one patient had a malignant adrenal tumor and abdominal paraganglioma. In the patient with the chemodectoma, a cerebellar hemagioblastoma became manifest 25 yr after his initial diagnosis with pheochromocytoma, leading only then to a clinical diagnosis of von Hippel-Lindau disease (VHL). A mutational analysis of the VHL gene revealed a novel nucleotide 709 G{r_arrow}T transversion present in all affected subjects and in four presymptomatic children. In familial pheochromocytoma the diagnosis of VHL should be considered, even when the formal criteria for diagnosis of the syndrome are lacking. 16 refs., 2 figs.

  12. 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.

  13. 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...

  14. Anesthesia for combined cesarean section and pheochromocytoma resection

    Directory of Open Access Journals (Sweden)

    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.

  15. Predictors of hemodynamic instability during surgery for pheochromocytoma.

    Science.gov (United States)

    Kiernan, Colleen M; Du, Liping; Chen, Xi; Broome, James T; Shi, Chanjuan; Peters, Mary F; Solorzano, Carmen C

    2014-11-01

    Resection of pheochromocytoma is often associated with hemodynamic instability (HDI). We examined patient and tumor factors that may influence HDI. The effect of pretreatment with nonselective α blockade phenoxybenzamine (PXB) versus selective α blockade on HDI and outcomes was also evaluated. The records of 91 patients who underwent adrenalectomy between 2002 and 2013 were retrospectively reviewed. HDI was determined by number of intraoperative episodes of systolic blood pressure (SBP) > 200 mmHg, those greater than or less than 30 % of baseline, heart rate > 110 bpm, and the need for postoperative vasopressors. Fishers exact, t test and regressions were performed. Among 91 patients, 78 % received PXB, 18 % selective α blockade and 4 % no adrenergic blockade. Patient demographics, tumor factors and surgical approach were similar among the blockade groups. On multivariate analysis, increasing tumor size was associated with a significant rise in the number of episodes of SBP > 30 % [rate ratio (RR) 1.40] and an increased postoperative vasopressor requirement [odds ratio (OR) 1.23]. Open adrenalectomy and use of selective blockade were associated with an increased number of episodes of SBP > 200 mmHg (RR 27.8 and RR 20.9, respectively). Open adrenalectomy was also associated with increased readmissions (OR 12.3), complications (OR 5.6), use of postoperative vasopressors (OR 4.4) and hospital stay (4.6 days longer). There were no differences in other HDI measurements or postoperative outcomes among the blockade groups. Tumor size, open adrenalectomy, and type of α blockade were associated with intraoperative HDI during pheochromocytoma resection. Selective blockade was associated with significantly more episodes of intraoperative hypertension but no perioperative adverse outcomes.

  16. Thunderclap-like headache triggered by micturition and angina as an initial manifestation of bladder pheochromocytoma. A case report

    Directory of Open Access Journals (Sweden)

    You Jin Han

    Full Text Available CONTEXT: Pheochromocytoma is a catecholamine-producing tumor characterized by hypertension, headache, tachycardia, excessive diaphoresis and angina. The thunderclap headache is so named because the pain strikes suddenly and severely. Although the symptoms of bladder pheochromocytoma are rather evident, the diagnosis of this rare neuroendocrine tumor can be missed. CASE REPORT: This study reports the case of a woman diagnosed with bladder pheochromocytoma who experienced thunderclap headache triggered by micturition and angina as an initial manifestation. CONCLUSION: This case study suggests that thunderclap headache and angina occurring concurrently with sudden blood pressure elevation during or immediately after micturition are important diagnostic clues for bladder pheochromocytoma.

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

    Science.gov (United States)

    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.

  18. Cardiorespiratory crisis at the end of pregnancy: a case of pheochromocytoma.

    Science.gov (United States)

    Haddad, Samir; Al-Raiy, Basel; Madkhali, Azza; Al-Qahtani, Saad; Al-Sultan, Mohammad; Arabi, Yaseen

    2013-06-01

    Pheochromocytoma during pregnancy is extremely rare. Its clinical manifestation includes hypertension with various clinical presentations, possibly resembling those of pregnancy-induced hypertension. The real challenge for clinicians is differentiating pheochromocytoma from other causes of hypertension (preeclampsia, gestational hypertension, and pre-existing or essential hypertension), from other cause of pulmonary edema (preeclampsia, peripartum cardiomyopathy, stress or Takotsubo cardiomyopathy, pre-existing cardiac disease [mitral stenosis], and high doses betamimetics), and from other causes of cardiovascular collapse (pulmonary embolism, and amniotic fluid embolism). Although, several cases of pheochromocytoma during pregnancy have been published, fetal and maternal mortalities due to undiagnosed cases are still reported. We report a case of a patient whose delivery by cesarean section was complicated by severe hemodynamic instability resulting in a cardiac arrest. Later on, pheochromocytoma was suspected based on computed tomography (CT) scan findings. Diagnosis was confirmed with special biochemical investigations that showed markedly elevated catecholamines in urine and metanephrines in serum, and later by histopathology of the excised left adrenal mass. This case illustrates the difficulty of diagnosing pheochromocytoma in pregnancy and raises the awareness to when this rare disease should be suspected.

  19. 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.

  20. Tetralogy of Fallot and pheochromocytoma in a situs inversus totalis: An unusual association.

    Science.gov (United States)

    Tapia-Orihuela, Rubén Kevin Arnold; Huaringa-Marcelo, Jorge; Loja-Oropeza, David

    2016-01-01

    Introduction: Situs inversus totalis is an uncommon anomaly which exist a complete transposition of organs and it's occasionally associated with congenital heart diseases, such as tetralogy of fallot. Pheochromocytoma is a rare neuroendocrine tumor with an annual incidence of 2-8 cases per million people and for years has been studied its relationship with the hypoxic pathway. Case Report: A 29 year old male with a history of tetralogy of fallot corrected at 10 years and situs inversus totalis. He was admitted to hospital with a progressive story of four months of constipation, palpitations, headache, dyspnea and sweating. Physical examination revealed a thinned man with peripheral cyanosis, clubbing and signs of decompensated congestive heart failure as hepatomegaly, legs edema, multifocal systodiastolic murmurs, abdominal distension and jugular venous distention. The echocardiogram shows severe right ventricular dysfunction and severe pulmonary hypertension. Furthermore, abdominal computed tomography shows right adrenal mass. Elevated metanephrines and catecholamines confirmed the diagnosis of pheochromocytoma. Surgical removal is decided and preoperative management begins with alpha-adrenergic blockade, however the patient had a hemodynamic decompensation with an unfavorable evolution. Discussion: In conclusion, there are few reports of cyanotic congenital heart disease with pheochromocytoma. Several studies show a significant association between both of them due to chronic hypoxia leads sustained hyperresponsiveness in adrenal medulla and it would cause the tumor. Special preoperative management of pheochromocytoma is recommended when there underlying heart disease and congestive heart failure. We present the first international report of tetralogy of fallot and pheochromocytoma in a patient with situs inversus totalis.

  1. Surgical Treatment of Malignant Pheochromocytoma and Paraganglioma: Retrospective Case Series.

    Science.gov (United States)

    Strajina, Veljko; Dy, Benzon M; Farley, David R; Richards, Melanie L; McKenzie, Travis J; Bible, Keith C; Que, Florencia G; Nagorney, David M; Young, William F; Thompson, Geoffrey B

    2017-06-01

    Pheochromocytoma and paraganglioma (PPGL) are rare neoplasms; about 10% are malignant. Literature regarding possible benefit from resection is extremely limited. A 20 year review of all patients undergoing surgery for malignant PPGL at the Mayo Clinic Rochester Campus between 1994 and June 2014 was performed. We identified 34 patients undergoing surgery for malignant PPGL. Median follow up was 6 and 5 years survival was 90% (median 11 years). Complete resection (R0) was achieved in 14 patients (41%). Median disease-free survival was 4.6 years for patients with R0 resection (up to 12 years). Only eight patients (23%) were disease-free on last follow up. Elevated preoperative fractionated metanephrines or catecholamines were documented in 23 patients (68%); these normalized in 13 of 23 patients (56%) postoperatively-with symptom relief in 15 of 18 preoperatively symptomatic patients (79%). Among 23 patients with hormone-producing tumors, significant reduction in number of antihypertensive medications was also noted postoperatively; 11 patients have remained off all antihypertensives, 6 required 1 medication, 1 required 2, while 5 required full blockade with phenoxybenzamine and a beta-adrenergic blocker. Surgery plays a significant role in the management of selected malignant PPGL. Resection can be effective in normalizing or significantly reducing levels of catecholamines and metanephrines, and can improve hormone-related symptoms and hypertension. Surgical resection, either complete or incomplete, is associated with durable survival despite a high rate of tumor recurrence.

  2. 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

  3. Cardiovascular collapse after labetalol for hypertensive crisis in an undiagnosed pheochromocytoma during cesarean section.

    Science.gov (United States)

    Kuok, Chi-Hang; Yen, Chia-Rong; Huang, Chong-Sin; Ko, Yuan-Pi; Tsai, Pei-Shan

    2011-06-01

    Pheochromocytoma is a catecholamine-producing tumor but rarely delayingly diagnosed until during pregnancy. We reported a pregnant woman who underwent emergent cesarean section because of intrauterine growth retardation, oligohydramnios, and hypertension. The existence of an undiagnosed pheochromocytoma was suspected by the unusual hemodynamic response to spinal anesthesia, abdominal compressions, and operative stimulus. Hypertensive crisis occurred during the operation and she was sent to the intensive care unit for postoperative care. In the intensive care unit, cardiovascular collapse occurred after nonselective β-adrenergic blockade. Unexpected hypertensive crisis during the perioperative period should alert clinicians to the possibility of a pheochromocytoma. For the treatment of choice, nonselective β-adrenergic blockade should not be used before the α-blockade. Copyright © 2011. Published by Elsevier B.V.

  4. 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.

  5. Neuron-specific enolase is a useful maker of neuroendocrine origin in pheochromocytoma cell culture

    International Nuclear Information System (INIS)

    Abelin, N.; Dahia, P.L.M.; Martin, R.; Kato, S.; Toledo, S.P.A.

    1994-01-01

    Neuron-specific enolase (NSE) has been used as a marker for neuroendocrine tumors either in immunocytochemical studies or in serum measurements. In this paper NSE levels were determined in cultured pheochromocytoma cells to test whether it is also a useful marker in cell culture of tumors derived from neuroendocrine system. Cultured pheochromocytoma cells came from a primary explant and were grown in RPMI supplemented with 20% fetal calf serum, 100 μg/mL ampicillin and 100 μ/mL streptomycin. NSE was measured in culture medium and cell homogenates. Samples from different pheochromocytoma cultures were analyzed and compared to normal cultured fibroblast cells derived from human skin. NSE was measured by a commercially available radioimmunoassay kit. NSE levels were higher in cell homogenates as compared to those in culture medium, reaching levels as high as 6-fold in the former in TE cell line (26.46 ng/mL and 4.39 ng/mL, respectively). Serial measurements in culture medium from TE cell line evidenced decreasing values in subsequential subcultures (from 9.24 ng/mL during primary explant to 1.7 ng/mL in the tenth subculture). In cultured normal fibroblasts, NSE levels in cultured media were definitely lower than those obtained from pheochromocytoma cultures. These preliminary data suggest that NSE may be a useful marker of neuroendocrine derived tumors, such as pheochromocytoma, in culture. Thus, the simplicity and availability of NSE radioimmunoassay provides an alternative to catecholamine measurement to better characterize pheochromocytoma cell lines in culture, with the advantage of faster result at lower costs. (author). 18 refs, 2 tabs

  6. Unsuspected pheochromocytoma: Risk of blood-pressure alterations during percutaneous adrenal biopsy

    Energy Technology Data Exchange (ETDEWEB)

    Casola, G.; Nicolet, V.; van Sonnenberg, E.; Withers, C.; Bretagnolle, M.; Saba, R.M.; Bret, P.M.

    1986-06-01

    Four unsuspected pheochromocytomas were discovered during percutaneous fine-needle biopsy of the adrenal gland under ultrasound (n = 1) and computed tomographic (n = 3) guidance. One patient suffered an acute episode of alternating hypertension and hypotension during the procedure. A second patient had no alterations in vital signs during the procedure but had a severe hypertensive crisis during induction of anesthesia at surgery. Neither biopsy nor surgery affected the vital signs in the other two patients. During biopsy study of adrenal lesions, the possibility of unsuspected pheo-chromocytoma should be considered, and the interventional radiologist must be familiar with the emergency treatment of hypotensive or hypertensive crises that may occur.

  7. Ultrasonography and radiocholesterol scintigraphy in the topographic diagnosis of a pheochromocytoma

    International Nuclear Information System (INIS)

    Chatal, J.F.; Vasseur, F.; Talmant, C.; Grolleau, B.; Lucas, J.; Charbonnel, B.

    1979-01-01

    Topographic diagnosis of adrenal pheochromocytoma was determined by ultrasonography in all 6 cases studied and by radiocholesterol scintigraphy in 6 out 7 cases studied. It would appear that ultrasonography is preferable in the localization of an abdominal pheochromocytoma, whether adrenal or extra-adrenal. Intravenous urography along with rapid sequence nephrotomography and radiocholesterol scintigraphy, play a complementary role in confirming the topographic diagnosis. In case these methods prove unsuccessful or provide conflicting results, it is then possible to consider computed tomography, angiography and canal catheterization [fr

  8. A Rare Coexistence of Pheochromocytoma and Parkinson's Disease With Diagnostic Challenges.

    Science.gov (United States)

    Matsumura-Matsuda, Erika; Sekiya, Motohiro; Omoto-Inuzuka, Miyoko; Santo, Kana; Shikama, Akito; Kuba, Motoko; Sugano, Yoko; Iwasaki, Hitoshi; Yatoh, Shigeru; Sato, Taiki; Hara, Hisato; Takekoshi, Kazuhiro; Suzuki, Hiroaki; Shimano, Hitoshi

    2018-04-01

    We herein report a case of pheochromocytoma occurring in the course of Parkinson's disease. The coexistence of these two disease is extremely rare, with only four cases hitherto reported across the public databases. It is also noteworthy that biochemical tests, which are critical for the diagnosis of pheochromocytoma, are severely confounded by dopaminergic medications for Parkinson's disease, highlighting the importance of image-based modalities in this setting. We further attempted to gain insight into the potential molecular mechanisms, proposing that hypoxia-inducible factor signaling could make these two diseases mutually exclusive, while excessive reactive oxygen species could enable their coexistence.

  9. 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

  10. SDH Subunit Mutation Status in Saliva : Genetic Testing in Patients with Pheochromocytoma

    NARCIS (Netherlands)

    Osinga, T E; Xekouki, P; Nambuba, J; Faucz, F R; de la Luz Sierra, M; Links, T P; Kema, I P; Adams, K; Stratakis, C A; van der Horst-Schrivers, A N A; Pacak, K

    Germline mutations occur in up to 30-40% of pheochromocytoma/paraganglioma, with mutations in the succinate dehydrogenase (SDH) subunits B (SDHB) and D (SDHD) being the most common. Blood samples are favored for obtaining high quality DNA, however, leukocytes can also be obtained by collecting

  11. POTENTIAL MECHANISMS RESPONSIBLE FOR CHLOROTRIAZINE-INDUCED ALTERATIONS IN CATECHOLAMINES IN PHEOCHROMOCYTOMA (PC12) CELLS

    Science.gov (United States)

    ABSTRACTPotential Mechanisms Responsible for Chlorotriazine-induced Changes in Catecholamine Metabolism in Pheochromocytoma (PC12) Cells*PARIKSHIT C. DAS1, WILLIAM K. McELROY2 , AND RALPH L. COOPER2+ 1Curriculum in Toxicology, University of North Carolina, Chape...

  12. 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.)

  13. Intraoperative hypertensive crisis secondary to an undiagnosed pheochromocytoma during orthognathic surgery: a case report.

    Science.gov (United States)

    Bouchard, Carl; Chiniara, Gilles; Valcourt, Annie-Claude

    2014-04-01

    Increased blood pressure (BP) during orthognathic surgery may result in excessive blood loss, poor surgical field visualization, and longer surgical time and require blood transfusion. When uncontrollable high BP is encountered in an otherwise healthy patient during orthognathic surgery, the diagnosis of pheochromocytoma should be considered. Pheochromocytomas are rare neuroendocrine tumors of the chromaffin cells of the adrenal medulla or extra-adrenal paraganglia (sympathetic ganglia) that secrete catecholamine. They are present in approximately 0.05 to 0.2% of hypertensive patients. Patients can present with hypertension, tachycardia, headaches, and diaphoresis. The clinical presentation may vary and a wide spectrum of nonspecific symptoms may be encountered. The elevated BP can be intermittent (40%) or permanent (60%). About 10% of pheochromocytomas are hereditary and they can be a feature of multiple endocrine neoplasia type 2. This report describes the case of a 29-year-old patient with a large pheochromocytoma of the right adrenal gland undiagnosed before orthognathic surgery. Copyright © 2014 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  14. Systematic genetic screening in a prospective group of Danish patients with pheochromocytoma

    DEFF Research Database (Denmark)

    Hansen, Morten Steen Svarer; Jacobsen, Niels; Frederiksen, Anja Lisbeth

    2017-01-01

    for mutations in the VHL, RET, SDHB, SDHC, and SDHD genes. A total of 41 patients were included, and genetic data were available in 35. In four of the 35 patients, a pathogenic variant was identified prior to the diagnosis of pheochromocytoma (von Hippel-Lindau disease, n=2; neurofibromatosis type 1, n=2...

  15. Genotype-Dependent Brown Adipose Tissue Activation in Patients With Pheochromocytoma and Paraganglioma

    NARCIS (Netherlands)

    Puar, T.; Berkel, A van; Gotthardt, M.; Havekes, B.; Hermus, A.R.M.M.; Lenders, J.W.M.; Marken-Lichtenbelt, W.D. van; Xu, Y.; Brans, B.; Timmers, H.J.L.M.

    2016-01-01

    CONTEXT: Patients with pheochromocytomas and paragangliomas (PGLs) may have brown adipose tissue (BAT) activation induced by catecholamine excess. (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET)/computed tomography (CT) can be used for the localization of both PGLs and BAT.

  16. 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

  17. Acute coronary syndrome: a rare case of multiple endocrine neoplasia syndromes with pheochromocytoma and medullary thyroid carcinoma.

    Science.gov (United States)

    Maloberti, Alessadro; Meani, Paolo; Pirola, Roberto; Varrenti, Marisa; Boniardi, Marco; De Biase, Anna Maria; Vallerio, Paola; Bonacina, Edgardo; Mancia, Giuseppe; Loli, Paola; Giannattasio, Cristina

    2015-09-01

    Pheochromocytoma is a tumor arising from neuroectodermal chromaffin tissues in the adrenal gland or extra-adrenal paraganglia (paragangliomas). The prevalence of the tumor is 0.1%-0.6% in the hypertensive population, of which 10%-20% are malignant. Pheochromocytoma produces, stores, and secretes catecholamines, as well as leads to hypertensive crisis, arrhythmia, angina, and acute myocardial infarction without coronary artery diseases. We report a case of acute coronary syndrome (ACS) with a final diagnosis of multiple endocrine neoplasia with pheochromocytoma and medullary thyroid carcinoma (MTC).

  18. Preoperative risk factors for haemodynamic instability during pheochromocytoma surgery in Chinese patients.

    Science.gov (United States)

    Jiang, Minchun; Ding, Huanyu; Liang, Ying; Tang, Juying; Lin, Ying; Xiang, Kexu; Guo, Ying; Zhang, Shaoling

    2018-03-01

    Pheochromocytoma surgery carries a high risk of haemodynamic instability (HI). However, there are few studies investigating the risk factors for HI for pheochromocytoma surgery in a Chinese population. Therefore, our objective was to identify preoperative risk factors for HI during surgery in a Chinese population with pheochromocytoma. In this retrospective study, 134 patients undergoing surgery for pheochromocytoma at a single university-affiliated hospital between November 2002 and July 2017 were enrolled. Demographics, comorbidities, preoperative medical preparation, operation details and perioperative haemodynamics of these patients were retrospectively collected and analysed. Multivariable logistic regression analysis was performed to identify the preoperative risk factors for intraoperative HI. 32.8% (44/134) patients suffered from intraoperative HI. According to the result of multivariate analysis, tumour diameter >50 mm (odds ratio [OR] 2.526; 95% confidence interval [CI] 1.163-5.485; P = .019), diabetes/prediabetes (OR 2.251; 95% CI 1.039-4.876; P = .040) and preoperative systolic blood pressure fluctuation >50 mm Hg (OR 3.163; 95% CI 1.051-9.522, P = .041) were independent predictors for intraoperative HI. The observed incidence of HI was 8.9%, 42.6%, 47.8% and 60% when zero, one, two or three risk factors were present, respectively. HI is common among Chinese patients undergoing surgery for pheochromocytoma. Our study identified three predictive factors for intraoperative HI: a large tumour diameter, diabetes/prediabetes and a great preoperative systolic blood pressure fluctuation. Furthermore, patients are more likely to suffer from HI when they have more predictive risk factors. Identification of these risk factors can help to improve perioperative management. © 2018 John Wiley & Sons Ltd.

  19. Tetralogy of Fallot and pheochromocytoma in a situs inversus totalis: An unusual association

    Directory of Open Access Journals (Sweden)

    Rubén Kevin Arnold Tapia Orihuela

    2016-09-01

    Full Text Available Introduction: Situs inversus totalis is an uncommon anomaly which exist a complete transposition of organs and it’s occasionally associated with congenital heart diseases, such as tetralogy of fallot. Pheochromocytoma is a rare neuroendocrine tumor with an annual incidence of 2-8 cases per million people and for years has been studied its relationship with the hypoxic pathway. Case Report: A 29 year old male with a history of tetralogy of fallot corrected at 10 years and situs inversus totalis. He was admitted to hospital with a progressive story of four months of constipation, palpitations, headache, dyspnea and sweating. Physical examination revealed a thinned man with peripheral cyanosis, clubbing and signs of decompensated congestive heart failure as hepatomegaly, legs edema, multifocal systodiastolic murmurs, abdominal distension and jugular venous distention. The echocardiogram shows severe right ventricular dysfunction and severe pulmonary hypertension. Furthermore, abdominal computed tomography shows right adrenal mass. Elevated metanephrines and catecholamines confirmed the diagnosis of pheochromocytoma. Surgical removal is decided and preoperative management begins with alpha-adrenergic blockade, however the patient had a hemodynamic decompensation with an unfavorable evolution. Discussion: In conclusion, there are few reports of cyanotic congenital heart disease with pheochromocytoma. Several studies show a significant association between both of them due to chronic hypoxia leads sustained hyperresponsiveness in adrenal medulla and it would cause the tumor. Special preoperative management of pheochromocytoma is recommended when there underlying heart disease and congestive heart failure. We present the first international report of tetralogy of fallot and pheochromocytoma in a patient with situs inversus totalis.

  20. Bilateral papillopathy as a presenting sign of pheochromocytoma associated with von Hippel–Lindau disease

    Directory of Open Access Journals (Sweden)

    Shah V

    2014-03-01

    Full Text Available Veeral Shah, Leonid Zlotcavitch, Angela M Herro, Sander R Dubovy, Zohar Yehoshua, Byron L LamBascom Palmer Eye Institute, University of Miami, Miller School of Medicine, Miami, FL, USAAbstract: A 7-year-old girl presented with decreased vision in both eyes for 1 month. Examination showed visual acuity of 20/50 and 20/60, no afferent pupillary defect, cecocentral scotomas, and bilateral optic disc edema with extensive peripapillary and macular exudates. Magnetic resonance imaging showed multiple cortical and subcortical white matter lesions. Both the laboratory workup and the systemic examination were unrevealing. However, on follow-up, the patient showed episodic elevations of blood pressure as high as 240/160. Further workup revealed elevated urine catecholamines and a right supra-adrenal mass proven to be a pheochromocytoma by histopathologic analysis. The paroxysmal hypertension resolved, and the visual acuity, visual fields, fundus exam, and neuroimaging improved. The patient was lost to follow-up until age 18 when she developed shortness of breath and was found to have multiple pulmonary metastases identified as pheochromocytoma by biopsy. Genetic testing identified a 3p25-26 (c.482 G>A VHL gene chromosomal mutation consistent with von Hippel–Lindau disease genotype. Multiple peripheral retinal vascular dilations and small retinal capillary hemangioblastomas were also found. This case highlights the importance of recognizing the lability of blood pressure often seen with pheochromocytomas, which may mask the underlying cause of hypertensive papillopathy and retinopathy, a diagnosis of low clinical suspicion in the pediatric population. The case also underscores the importance of thorough systemic workup, including genotyping to detect conditions where pheochromocytoma may be the presenting sign of the disease, such as multiple endocrine neoplasia 2A and 2B, von Hippel–Lindau disease, von Recklinghausen disease, tuberous sclerosis, and

  1. Genotype-specific differences in the tumor metabolite profile of pheochromocytoma and paraganglioma using untargeted and targeted metabolomics

    NARCIS (Netherlands)

    Rao, J.U.; Engelke, U.F.H.; Sweep, F.C.; Pacak, K.; Kusters, B.; Goudswaard, A.G.; Hermus, A.R.M.M.; Mensenkamp, A.R.; Eisenhofer, G.; Qin, N.; Richter, S; Kunst, H.P.M.; Timmers, H.J.L.M.; Wevers, R.A.

    2015-01-01

    CONTEXT AND OBJECTIVE: Pheochromocytomas and paragangliomas (PGLs) are neuroendocrine tumors of sympathetic or parasympathetic paraganglia. Nearly 40% of PGLs are caused by germline mutations. The present study investigated the effect of genetic alterations on metabolic networks in PGLs. DESIGN:

  2. Staging and functional characterization of pheochromocytoma and paraganglioma by 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography.

    NARCIS (Netherlands)

    Timmers, H.J.L.M.; Chen, C.C.; Carrasquillo, J.A.; Whatley, M.; Ling, A.; Eisenhofer, G.; King, K.S.; Rao, J.U.; Wesley, R.A.; Adams, K.T.; Pacak, K.

    2012-01-01

    BACKGROUND: Pheochromocytomas and paragangliomas (PPGLs) are rare tumors of the adrenal medulla and extra-adrenal sympathetic chromaffin tissues; their anatomical and functional imaging are critical to guiding treatment decisions. This study aimed to compare the sensitivity and specificity of

  3. 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

  4. 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

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

    Science.gov (United States)

    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.)

  6. Synchronous bilateral pheochromocytomas and paraganglioma with novel germline mutation in MAX: a case report.

    Science.gov (United States)

    Shibata, Masahiro; Inaishi, Takahiro; Miyajima, Noriyuki; Adachi, Yayoi; Takano, Yuko; Nakanishi, Kenichi; Takeuchi, Dai; Noda, Sumiyo; Aita, Yuichi; Takekoshi, Kazuhiro; Kodera, Yasuhiro; Kikumori, Toyone

    2017-12-28

    Recent advance of genetic testing has contributed to the diagnosis of hereditary pheochromocytoma and paraganglioma (PPGL). The clinical characteristics of hereditary PPGL are varying among the types of mutational genes. It is still difficult to specify the pathognomonic symptoms in the case of rare genetic mutations. Here, we report the case of synchronous bilateral pheochromocytomas and paraganglioma with novel MYC associated factor X (MAX) gene mutation. A 24-year-old female had hyperhidrosis and hypertension. Her urine test showed high normetanephrine and vanillylmandelic acid. Enhanced computed tomography revealed three enhanced masses in right adrenal gland, left adrenal gland, and left renal hilus. She was diagnosed with PPGL. Because 123 I-metaiodobenzylguanidine scintigraphy indicated the accumulations in the left adrenal gland mass and the left renal hilus mass and not in the right adrenal gland mass, we performed laparoscopic left adrenalectomy and extirpation of the left renal hilus mass to preserve the right adrenocortical function. However, her symptoms recurred shortly after the operation presumably due to unveiling of the activity of the right pheochromocytoma. Following right adrenalectomy as the second operation, the catecholamine levels declined to normal range. Her genetic testing indicated the novel germline mutation in MAX gene (c.70_73 del AAAC/p.Lys24fs*40). MAX germline mutation is recently identified as a rare cause of hereditary PPGL. The deletion mutation in MAX gene in this patient has never reported before. In the case of bilateral pheochromocytomas, the surgical indication should be decided considering each patient's genetic background. Due to the possibility for other types of malignant tumors, close follow-up is essential for MAX mutation carriers.

  7. Perianesthetic management of the first robotic partial cystectomy in bladder pheochromocytoma. A case report.

    Science.gov (United States)

    Pandey, R; Garg, R; Roy, K; Darlong, V; Punj, J; Kumar, A

    2010-04-01

    The authors report the perianesthetic considerations of a rare case of pheochromocytoma of the urinary bladder for which the first reported robotic partial cystectomy and ureteric reimplantation were performed. A 59-year-old male patient, known to be hypertensive, was posted for transurethral resection of a bladder tumor. In the operation room, after attaching the monitors, a subarachnoid block was given. Upon manipulation of the tumor, the blood pressure and heart rate increased markedly. A pheochromocytoma was suspected and was later confirmed by raised urine catecholamine levels and meta-iodobenzyl-guanidine scan. The patient was started on tablet prazosin and atenolol. After optimization, a robotic partial cystectomy was planned. In the operating room, an epidural catheter and a radial artery cannula were inserted. After the induction of anesthesia and the securing of the airway, surgery was started. After the insertion of the verres needle, pneumoperitoneum was created very slowly, and then the patient was positioned in 40 degrees Trendelenburg. Surges in arterial blood pressure (ABP) were managed with titrated doses of sodium nitroprusside and nitroglycerine and boluses of esmolol and labetalol. ABP drops postoperatively were managed with fluid and dopamine infusion. Robotic surgery is a safe alternative to the open technique for pheochromocytoma of the urinary bladder. Care should be taken during the positioning of the patient for robot placement and during pneumoperitoneum creation.

  8. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Acutely exacerbated hypertension and increased inflammatory signs due to radiation treatment for metastatic pheochromocytoma

    International Nuclear Information System (INIS)

    Teno, Shinichi; Tanabe, Akiyo; Nomura, Kaoru; Demura, Hiroshi

    1996-01-01

    Hypertension and norepinephrine hypersecretion in a 59-year-old woman suffering from malignant pheochromocytoma with multiple metastases were appropriately controlled with α- and β- blockers, and α-methyltyrosine (α-MT), a catecholamine-synthesis inhibitor. Metastasized vertebrae were treated with external radiation to relieve pain, but this treatment had to be interrupted at a total dose of 20 Gy because the patient suffered acutely exacerbated hypertension (200/110 mmHg), tachycardia (160 beats/min) and a low-grade fever. Simultaneously her serum levels of LDH, potassium, urea nitrogen, creatinine, white blood cell count, CRP and norepinephrine were significantly increased, suggesting that this episode was due to radiation-induced tissue destruction and the leakage of catecholamines and possibly interleukin-6, a cytokine mediating inflammation which is reportedly present in pheochromocytoma. The marked hypertension was controlled by continuous iv administration of phentolamine and propranolol. Although radiation therapy effectively relieves pain due to neoplasmic metastasis to the bone, physicians should be aware that life-threatening complications such as the above occur in malignant pheochromocytoma. Sufficient pretreatment with adrenergic blocking agents and/or α-MT and careful monitoring of the patient's general condition during radiation therapy, even at a low dose, are highly recommended. (author)

  11. 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.

  12. Spectrum and prevalence of FP/TMEM127 gene mutations in pheochromocytomas and paragangliomas.

    Science.gov (United States)

    Yao, Li; Schiavi, Francesca; Cascon, Alberto; Qin, Yuejuan; Inglada-Pérez, Lucia; King, Elizabeth E; Toledo, Rodrigo A; Ercolino, Tonino; Rapizzi, Elena; Ricketts, Christopher J; Mori, Luigi; Giacchè, Mara; Mendola, Antonella; Taschin, Elisa; Boaretto, Francesca; Loli, Paola; Iacobone, Maurizio; Rossi, Gian-Paolo; Biondi, Bernadette; Lima-Junior, José Viana; Kater, Claudio E; Bex, Marie; Vikkula, Miikka; Grossman, Ashley B; Gruber, Stephen B; Barontini, Marta; Persu, Alexandre; Castellano, Maurizio; Toledo, Sergio P A; Maher, Eamonn R; Mannelli, Massimo; Opocher, Giuseppe; Robledo, Mercedes; Dahia, Patricia L M

    2010-12-15

    Pheochromocytomas and paragangliomas are genetically heterogeneous neural crest-derived neoplasms. We recently identified germline mutations of the novel transmembrane-encoding gene FP/TMEM127 in familial and sporadic pheochromocytomas consistent with a tumor suppressor effect. To examine the prevalence and spectrum of FP/TMEM127 mutations in pheochromocytomas and paragangliomas and to test the effect of mutations in vitro. We sequenced the FP/TMEM127 gene in 990 individuals with pheochromocytomas and/or paragangliomas, including 898 previously unreported cases without mutations in other susceptibility genes from 8 independent worldwide referral centers between January 2009 and June 2010. A multiplex polymerase chain reaction-based method was developed to screen for large gene deletions in 545 of these samples. Confocal microscopy of 5 transfected mutant proteins was used to determine their subcellular localization. The frequency and type of FP/TMEM127 mutation or deletion was assessed and correlated with clinical variables; the subcellular localization of 5 overexpressed mutants was compared with wild-type FP/TMEM127 protein. We identified 19 potentially pathogenic FP/TMEM127 germline mutations in 20 independent families, but no large deletions were detected. All mutation carriers had adrenal tumors, including 7 bilateral (P = 2.7 × 10(-4)) and/or with familial disease (5 of 20 samples; P = .005). The median age at disease onset in the FP/TMEM127 mutation group was similar to that of patients without a mutation (41.5 vs 45 years, respectively; P = .54). The most common presentation was that of a single benign adrenal tumor in patients older than 40 years. Malignancy was seen in 1 mutation carrier (5%). Expression of 5 novel FP/TMEM127 mutations in cell lines revealed diffuse localization of the mutant proteins in contrast with the discrete multiorganelle distribution of wild-type TMEM127. Germline mutations of FP/TMEM127 were associated with pheochromocytoma but

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

    Directory of Open Access Journals (Sweden)

    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.

  14. 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

  15. Adrenal Incidentaloma Diagnosed as a Pheochromocytoma in a fifteen-year-old Dog - An Unexpected Finding with Deadly Consequences

    Directory of Open Access Journals (Sweden)

    R Seixas and AM Alho*

    2013-11-01

    Full Text Available Adrenal incidentalomas are masses of the adrenal gland discovered inadvertently during diagnostic procedures, from which a significant percentage are pheochromocytomas and these tumors are rare. Here we report a case of a 15-year-old male dog whose main complaints were a soft cervical mass and mild generalized weakness. Blood cell count, routine biochemistry, arterial blood pressure and electrocardiogram were performed. Diagnostic imaging revealed a 3.5 cm mass next to the right adrenal gland. Surgery was performed and histopathology examination of the mass confirmed a malignant pheochromocytoma. The dog died 96 hours later after surgery. At necropsy, metastasis was found in cervical lymph node. Considering vague and episodic clinical signs, pheochromocytoma antemortem diagnosis is uncommon. The main aim of this case is to highlight this endocrinology disorder, increasing the awareness of clinicians to this difficult diagnostic condition.

  16. A Rare Case of Adrenal Pheochromocytoma with Unusual Clinical and Biochemical Presentation: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Waad-Allah S. Mula-Abed

    2015-09-01

    Full Text Available A 50-year-old Omani woman presented to the Outpatient Clinic, Royal Hospital, Oman with right upper abdominal pain and backache that had lasted 10 days. She had no palpitation, sweating, or hypertension (blood pressure 122/78mmHg. The patient’s history revealed that she had a similar incidence of abdominal pain two months prior, which was a "dull ache" in nature and somewhat associated with headache. The pain was relieved using a mild analgesic drug. Abdominal ultrasonography showed a right adrenal mass, and both computed tomography and magnetic resonance imaging of the adrenal glands confirmed a right adrenal mass consistent with adrenal pheochromocytoma. However, clinical biochemistry tests revealed normal levels of plasma catecholamines (dopamine, norepinephrine, and epinephrine and metanephrine, which are unusual findings in adrenal pheochromocytoma. Meanwhile, the patient had markedly raised plasma normetanephrine (10-fold which, together with the normal metanephrine, constitutes a metabolic profile that is compatible with extra-adrenal pheochromocytoma. The patient also had markedly raised chromogranin A (16-fold, consistent with the presence of a neuroendocrine tumor. Laparoscopic right adrenalectomy was done and the adrenal tumor was excised and retrieved in total. Histopathology and immunohistochemistry confirmed the diagnosis of adrenal pheochromocytoma; the tumor cells being positive for chromogranin, synaptophysin, and S-100 protein. Following surgery, the patient did well and showed full recovery at follow-up after three months. Molecular genetic testing showed no pathogenic mutation in pheochromocytoma genes: MAX, SDHA, SDHAF2, SDHB, SDHC, SDHD, VHL, and PRKAR1A. A review of the literature was conducted to identify the pathophysiology and any previous reports of such case. To our knowledge, this is the first report in Oman of the extremely rare entity of pheochromocytoma with an unusual clinical and biochemical scenario.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Use of the Esophageal Doppler Machine to help guide the intraoperative management of two children with pheochromocytoma.

    Science.gov (United States)

    Hack, Henrik

    2006-08-01

    The anesthetic management of pheochromocytoma has been based upon the intraoperative control of blood pressure and fluid balance following adequate preoperative preparation. This can be difficult, especially in the presence of significant comorbidity such as cardiac or renal dysfunction. Two cases of children with pheochromocytoma are reported where the introperative management of fluid balance and blood pressure control were guided by measurement of changes in descending aortic blood flow using an esophageal Doppler probe. The advantages of such a technique compared with more invasive monitors are discussed.

  19. 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...... 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....

  20. 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.

  1. ENDOCRINOLOGY IN PREGNANCY: Pheochromocytoma in pregnancy: case series and review of literature.

    Science.gov (United States)

    van der Weerd, K; van Noord, C; Loeve, M; Knapen, M F C M; Visser, W; de Herder, W W; Franssen, G; van der Marel, C D; Feelders, R A

    2017-08-01

    Pheochromocytoma in pregnancy is extremely rare. Early recognition is crucial as antepartum diagnosis can largely decrease maternal and fetal mortality rates. As symptoms of pheochromocytoma are rather similar to those of other far more common causes of hypertension during pregnancy, timely diagnosis is a challenge. In pregnant patients, similar to non-pregnant patients, increased plasma and/or 24-h urine (nor)metanephrine concentrations most reliably confirm the diagnosis of pheochromocytoma. MRI and ultrasound are the only imaging modalities that can be used safely during pregnancy to localize the tumor. During pregnancy, pretreatment consists of alpha blockade as usual. However, dosing of α-adrenergic receptor blockers during pregnancy is a challenge as hypertension must be treated while preserving adequate uteroplacental circulation. When the diagnosis is made within the first 24 weeks of pregnancy, it is generally recommended to remove the tumor in the second trimester, while resection is generally postponed till after delivery when the diagnosis is made in the third trimester and medical pretreatment is sufficient. Both during and after pregnancy, laparoscopic surgery is the preferred approach for resection of the tumor. There is no consensus in literature about the preferred route and timing of delivery. Therefore, in our opinion, decisions should be made on an individual basis by an experienced and dedicated multidisciplinary team. Over the last decades, maternal and fetal prognosis has improved considerably. Further increasing awareness of this rare diagnosis and treatment of these patients by a dedicated team in a tertiary referral hospital are critical factors for optimal maternal and fetal outcome. © 2017 European Society of Endocrinology.

  2. [Hereditary pheochromocytoma--a family affected by von Hippel-Lindau disease].

    Science.gov (United States)

    Mertl, J; Rovný, A; Krepelová, A; Prásek, J

    2003-07-01

    The authors present a case of a 37 year old male (proband) with a 13 year history of progressive sight impairment leading to blindness and a 4 year history of a mild hypertension. He was incidentally found to have large adrenal tumors after an ultrasound kidney examination. The tumors were confirmed with CT scan and magnetic resonance imaging. A bilateral pheochromocytoma was biochemically demonstrated and successfully removed. The eye diagnosis of angiomatosis retinae von Hippel-Lindau was ascertained after a search of the patient files in other medical departments, which led to a family screening. Proband's brother, having hypertension and a history of a cerebellar astrocytoma operation, was also diagnosed with CT scan to have a bilateral pheochromocytoma. Unfortunately, at the same time he was found to have a large irremovable neuroendocrine pancreatic carcinoma, which caused complications and his eventual death. Both proband and his brother were affected by the same CGG(Arg167)->CAG(Gln) mutation in the exon 3 of the VHL gene. Other living and examined family members were not affected, which was confirmed by negative genetic testing. One year after the pheochromocytoma operation, proband was diagnosed to have a retroperitoneal tumor left to the aorta, clinically silent, with slightly and non-constantly elevated urine norepinephrine and normetanephrine. Metaiodobenzylguanidine scintigraphy showed that it was a paraganglioma. The old CT and magnetic resonance picture review demonstrated that the tumor had already been present at the time of the operation. It was surgically removed and histologically verified. It is a pity that proband had not been sent by his ophthalmologist for an endocrine examination when the eye diagnosis was determined. Affection of the family would have been discovered earlier, and proband's brother might have possibly been saved.

  3. [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.

  4. Hypertensive crisis due to contrast-enhanced computed tomography in a patient with malignant pheochromocytoma.

    Science.gov (United States)

    Nakano, Sachiko; Tsushima, Yoshito; Taketomi-Takahashi, Ayako; Higuchi, Tetsuya; Amanuma, Makoto; Oriuchi, Noboru; Endo, Keigo

    2011-07-01

    A 63-year-old man underwent computed tomography (CT) using intravenous low-osmolar iodine contrast medium (LOCM) 6 days after undergoing high-dose (131)I-MIBG therapy for metastatic pheochromocytoma. Immediately after the CT examination, his blood pressure increased to 260/160 mmHg (from 179/101 mmHg before the examination). Phentolamine mesilate was administered, and the blood pressure rapidly went back to normal. Although hypertensive crisis after administration of LOCM is rare, this case suggests that high-dose (131)IMIBG therapy may be a risk factor for hypertensive crisis after administration of intravenous LOCM.

  5. 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.)

  6. Miocardiopatía dilatada y feocromocitoma Dilated myocardiopathy and pheochromocytoma

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  8. Hypertensive emergency due to pheochromocytoma crisis complicated with refractory hemodynamic collapse.

    Science.gov (United States)

    Hayıroğlu, Mert İlker; Yıldırımtürk, Özlem; Bozbay, Mehmet; Eren, Mehmet; Pehlivanoğlu, Seçkin

    2015-12-01

    Hypertensive emergency usually appears in older patients with previous recurrent episodes, and is among the most frequent admissions to emergency departments. A 29-year-old woman was referred to our clinic with the diagnosis of hypertensive emergency. The patient complained of severe headache, dyspnea, palpitation, diaphoresis, and confusion due to hypertensive encephalopathy. Her blood pressure was 250/150 mmHg on admission. At the referral hospital, the patient had undergone cranial CT because of her confused state and this excluded acute cerebral hemorrhage. Also at that hospital, thoracoabdominal CT for differential diagnosis depicted an adrenal mass with a necrotic core. After admission to our clinic, initial control of excessive blood pressure was not achieved despite high dose intravenous nitrate therapy. Thereafter intravenous esmolol treatment was initiated simultaneously with oral alpha blocker therapy in order to counterbalance the unopposed alpha adrenergic activity with beta blocker therapy. After 12 hours, sudden onset of hypotension developed and deepened despite IV saline, inotropic and vasopressor agents such as IV dopamine, noradrenaline and adrenaline. The patient died at the 24th hour due to hemodynamic collapse as a result of hyperadrenergic state due to possible pheochromocytoma crisis. This case is an exceptional example of hypertensive emergency secondary to fulminant pheochromocytoma crisis failing to respond to intensive antihypertensive treatment, and in which patient death was unavoidable due to uncontrolled excessive adrenergic activity which led to profound cardiogenic shock.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. 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

  11. Performance of plasma free metanephrines measured by liquid chromatography-tandem mass spectrometry in the diagnosis of pheochromocytoma

    NARCIS (Netherlands)

    Peaston, Robert T.; Graham, Kendon S.; Chambers, Erin; van der Molen, Jan C.; Ball, Stephen

    2010-01-01

    Background: Plasma free metanephrines have proved a highly sensitive biochemical test for the diagnosis or pheochromocytoma. We have developed and validated a simple, LC-MS/MS method to determine plasma metanephrines and compared the diagnostic efficacy of the method with an enzyme immunoassay

  12. 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)

  13. 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.

  14. MANGANESE-INDUCED RAT PHEOCHROMOCYTOMA (PC12) CELL DEATH IS INDEPENDENT OF CASPASE ACTIVATION. (R826248)

    Science.gov (United States)

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

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

    Directory of Open Access Journals (Sweden)

    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.

  16. 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.

  17. Clinically guided genetic screening in a large cohort of italian patients with pheochromocytomas and/or functional or nonfunctional paragangliomas.

    Science.gov (United States)

    Mannelli, Massimo; Castellano, Maurizio; Schiavi, Francesca; Filetti, Sebastiano; Giacchè, Mara; Mori, Luigi; Pignataro, Viviana; Bernini, Gianpaolo; Giachè, Valentino; Bacca, Alessandra; Biondi, Bernadette; Corona, Giovanni; Di Trapani, Giuseppe; Grossrubatscher, Erika; Reimondo, Giuseppe; Arnaldi, Giorgio; Giacchetti, Gilberta; Veglio, Franco; Loli, Paola; Colao, Annamaria; Ambrosio, Maria Rosaria; Terzolo, Massimo; Letizia, Claudio; Ercolino, Tonino; Opocher, Giuseppe

    2009-05-01

    The aim of the study was to define the frequency of hereditary forms and the genotype/phenotype correlations in a large cohort of Italian patients with pheochromocytomas and/or functional or nonfunctional paragangliomas. We examined 501 consecutive patients with pheochromocytomas and/or paragangliomas (secreting or nonsecreting). Complete medical and family histories, as well as the results of clinical, laboratory, and imaging studies, were recorded in a database. Patients were divided into different groups according to their family history, the presence of lesions outside adrenals/paraganglia considered syndromic for VHL disease, MEN2, and NF1, and the number and types of pheochromocytomas and/or paragangliomas. Germ-line mutations in known susceptibility genes were investigated by gene sequencing (VHL, RET, SDHB, SDHC, SDHD) or diagnosed according to phenotype (NF1). In 160 patients younger than 50 yr with a wild-type profile, multiplex ligation-dependent probe amplification assays were performed to detect genomic rearrangements. Germline mutations were detected in 32.1% of cases, but frequencies varied widely depending on the classification criteria and ranged from 100% in patients with associated syndromic lesions to 11.6% in patients with a single tumor and a negative family history. The types and number of pheochromocytomas/paragangliomas as well as age at presentation and malignancy suggest which gene should be screened first. Genomic rearrangements were found in two of 160 patients (1.2%). The frequency of the hereditary forms of pheochromocytoma/paraganglioma varies depending on the family history and the clinical presentation. A positive family history and an accurate clinical evaluation of patients are strong indicators of which genes should be screened first.

  18. Pheochromocytoma as a rare cause of arterial hypertension in a patient with autosomal dominant polycystic kidney disease: A diagnostic and therapeutic dilemma

    Directory of Open Access Journals (Sweden)

    Amelia J. Hessheimer

    2015-01-01

    Discussion & conclusion: Pheochromocytoma is a rare but treatable cause of hypertension in ADPKD; given the anatomical complexities these patients present, careful preoperative planning and surgical technique are essential to a favorable outcome.

  19. Genotype-specific abnormalities in mitochondrial function associate with distinct profiles of energy metabolism and catecholamine content in pheochromocytoma and paraganglioma

    NARCIS (Netherlands)

    Rao, J.U.; Engelke, U.F.H.; Rodenburg, R.J.T.; Wevers, R.A.; Pacak, K.; Eisenhofer, G.; Qin, N.; Kusters, B.; Goudswaard, A.G.; Lenders, J.W.M.; Hermus, A.R.M.M.; Mensenkamp, A.R.; Kunst, H.P.M.; Sweep, F.C.; Timmers, H.J.L.M.

    2013-01-01

    PURPOSE: Pheochromocytomas and paragangliomas (PGL) are neuroendocrine tumors of sympathetic and parasympathetic paraganglia. This study investigated the relationships between genotype-specific differences in mitochondrial function and catecholamine content in PGL tumors. EXPERIMENTAL DESIGN:

  20. 99mTc-HYNIC-TOC scintigraphy is superior to 131I-MIBG imaging in the evaluation of extraadrenal pheochromocytoma.

    Science.gov (United States)

    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.

  1. New Insights into the Nuclear Imaging Phenotypes of Cluster 1 Pheochromocytoma and Paraganglioma.

    Science.gov (United States)

    Taïeb, David; Pacak, Karel

    2017-11-01

    Pheochromocytomas and paragangliomas (PPGLs) belong to the family of neural crest cell-derived neoplasms. In up to 70% of cases they are associated with germline and somatic mutations in 15 well-characterized PPGL driver or fusion genes. PPGLs can be grouped into three main clusters, where cluster 1 includes PPGLs characterized by a pseudohypoxic signature. Although cluster 1 tumors share several common features, they exhibit unique behaviors. We present here unique insights into the imaging phenotypes of cluster 1 PPGLs based on glucose uptake, catecholamine metabolism, and somatostatin receptor expression. Recent data suggest that succinate is a major player in the imaging phenotype of succinate dehydrogenase-deficient PPGLs. This review emphasizes the emerging stromal cell-succinate interaction and highlights new perspectives in PPGL theranostics. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Incidentally Detected Inoperable Malignant Pheochromocytoma with Hepatic Metastasis Treated by Transcatheter Arterial Chemoembolization

    Directory of Open Access Journals (Sweden)

    Joong Keun Kim

    2014-12-01

    Full Text Available Malignant pheochromocytoma (PCC is a rare condition. Although the liver is the second most frequent site of metastasis in malignant PCC, no definite treatments have been established. Herein, we report a case of liver metastasis of PCC that was successfully treated by transcatheter arterial chemoembolization (TACE. A 69-year-old man was admitted to the Department of Gastroenterology for evaluation of an incidental hepatic mass in August 2013. He had undergone right adrenalectomy in May 2005 and PCC had been confirmed on the basis of histopathological findings. Liver biopsy was performed, and metastatic PCC was diagnosed. The lesion appeared inoperable because of invasion of the portal vein and metastases in the lymph nodes along the hepatoduodenal ligament. Thus, TACE was performed instead. After TACE, symptoms including dizziness and cold sweating improved, and the patient's serum catecholamine levels decreased. On the basis of this case, we believe that TACE may be a useful treatment for liver metastasis in malignant PCC.

  4. INHIBITION OF HUMAN A7 NEURONAL NICOTINIC ACETYLCHOLINE RECEPTORS BY THE VOLATILE ORGANIC SOLVENT TRICHLOROETHYLENE.

    Science.gov (United States)

    Volatile organic compounds such as toleune, trichloroethylene and perchloroethylene are potent and reversible blockers of voltage-gated calcium current in nerve growth factor (NGF)-differentiated pheochromocytoma (PC12) cells. It is hypothesized that effects of VOCs on ICa contri...

  5. 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)

  6. Rats

    Directory of Open Access Journals (Sweden)

    Alexey Kondrashov

    2012-01-01

    Full Text Available We aimed to perform a chemical analysis of both Alibernet red wine and an alcohol-free Alibernet red wine extract (AWE and to investigate the effects of AWE on nitric oxide and reactive oxygen species production as well as blood pressure development in normotensive Wistar Kyoto (WKY and spontaneously hypertensive rats (SHRs. Total antioxidant capacity together with total phenolic and selected mineral content was measured in wine and AWE. Young 6-week-old male WKY and SHR were treated with AWE (24,2 mg/kg/day for 3 weeks. Total NOS and SOD activities, eNOS and SOD1 protein expressions, and superoxide production were determined in the tissues. Both antioxidant capacity and phenolic content were significantly higher in AWE compared to wine. The AWE increased NOS activity in the left ventricle, aorta, and kidney of SHR, while it did not change NOS activity in WKY rats. Similarly, increased SOD activity in the plasma and left ventricle was observed in SHR only. There were no changes in eNOS and SOD1 expressions. In conclusion, phenolics and minerals included in AWE may contribute directly to increased NOS and SOD activities of SHR. Nevertheless, 3 weeks of AWE treatment failed to affect blood pressure of SHR.

  7. Pheochromocytoma Crisis in the ICU: A French Multicenter Cohort Study With Emphasis on Rescue Extracorporeal Membrane Oxygenation.

    Science.gov (United States)

    Sauneuf, Bertrand; Chudeau, Nicolas; Champigneulle, Benoit; Bouffard, Claire; Antona, Marion; Pichon, Nicolas; Marrache, David; Sonneville, Romain; Marchalot, Antoine; Welsch, Camille; Kimmoun, Antoine; Bouchet, Bruno; Messai, Elmi; Ricome, Sylvie; Grimaldi, David; Chelly, Jonathan; Hanouz, Jean-Luc; Mercat, Alain; Terzi, Nicolas

    2017-07-01

    To describe the characteristics, management, and outcome of patients admitted to ICUs for pheochromocytoma crisis. A 16-year multicenter retrospective study. Fifteen university and nonuniversity ICUs in France. Patients admitted in ICU for pheochromocytoma crisis. None. We included 34 patients with a median age of 46 years (40-54 yr); 65% were males. At admission, the median Sequential Organ Failure Assessment score was 8 (4-12) and median Simplified Acute Physiology Score II 49.5 (27-70). The left ventricular ejection fraction was consistently decreased with a median value of 30% (15-40%). Mechanical ventilation was required in 23 patients, mainly because of congestive heart failure. Vasoactive drugs were used in 23 patients (68%) and renal replacement therapy in eight patients (24%). Extracorporeal membrane oxygenation was used as a rescue therapy in 14 patients (41%). Pheochromocytoma was diagnosed by CT in 33 of 34 patients. When assayed, urinary metanephrine and catecholamine levels were consistently elevated. Five patients underwent urgent surgery, including two during extracorporeal membrane oxygenation. Overall ICU mortality was 24% (8/34), and overall 90-day mortality was 27% (9/34). Crude 90-day mortality was not significantly different between patients managed with versus without extracorporeal membrane oxygenation (22% vs 30%) (p = 0.7) despite higher severity scores at admission in the extracorporeal membrane oxygenation group. Mortality is high in pheochromocytoma crisis. Routinely considering this diagnosis and performing abdominal CT in patients with unexplained cardiogenic shock may allow an earlier diagnosis. Extracorporeal membrane oxygenation and adrenalectomy should be considered as a therapeutic in most severe cases.

  8. 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.)

  9. The Importance of Exclusion of Obstructive Sleep Apnea During Screening for Adrenal Adenoma and Diagnosis of Pheochromocytoma

    Directory of Open Access Journals (Sweden)

    Alicia C. Weeks MD

    2015-09-01

    Full Text Available Context. As catecholamine elevation is a key element in the diagnosis of pheochromocytoma, more commonplace causes of sympathetic excess, such as obstructive sleep apnea (OSA, should be excluded as standard practice prior to diagnosis. This is essential to avoid misdiagnosis of adrenal incidentalomas identified in the estimated 42 million Americans with OSA, with greater than 4 million projected to undergo a computed tomography study annually. Case Description. A 56-year-old woman presented with a several year history of paroxysmal hypertension, palpitations, and diaphoresis. Abdominal/pelvic computed tomography performed during an unrelated hospitalization revealed a 2-cm left-sided adrenal nodule initially quantified at 37 Hounsfield units. Posthospitalization, 24-hour urine normetanephrine level was markedly elevated. Reassessment 2 weeks later revealed continued normetanephrine excess. Following normal thyroid function tests, morning cortisol, aldosterone, and plasma renin activity, laparoscopic adrenalectomy was performed. Surgical pathology identified an adrenal cortical adenoma. As paroxysms continued postoperatively, repeat 24-hour urine metanephrines were measured, demonstrating essentially unchanged normetanephrine elevation. Search for an alternate cause ensued, revealing OSA with progressive continuous positive airway pressure noncompliance over the preceding year. Regular continuous positive airway pressure therapy was resumed, and at the end of 7 weeks, 24-hour urine normetanephrine levels had declined. Conclusion. Pheochromocytomas are rare and sleep apnea is common. However, the overlap of clinical symptoms between these disorders is substantial, as is their ability to produce catecholamine excess. Thus, excluding uncontrolled or undiagnosed OSA in high-risk patients should be standard practice before diagnosing pheochromocytoma.

  10. Amoxicillin-associated interference in an HPLC-EC assay for urinary fractionated metanephrines: potential pitfall in pheochromocytoma biochemical diagnosis.

    Science.gov (United States)

    Barco, Sebastiano; Alpigiani, Maria Giannina; Ghiggeri, Gian Marco; Talio, Marina; Maffia, Angelo; Tripodi, Gino; Cangemi, Giuliana

    2014-10-01

    Measurement of urinary fractionated metanephrines represents a first-line test for the biochemical diagnosis of pheochromocytoma. The high performance liquid chromatography coupled to electrochemical detection (HPLC-EC) assays used in the routine clinical laboratory can be subjected to analytical interferences by the presence of drugs or their metabolites. In this paper we describe the interference on urinary normetanephrine (uNMN) caused by amoxicillin. Two pediatric patients suspected of pheochromocytoma had very high uNMN levels (2543 and 4227μg/g Cr respectively; upper reference value: 339μg/g Cr). Amoxicillin interference was assessed by comparison for co-elution with uNMN and by LC-MS/MS analysis. After amoxicillin interference was suspected and the therapy was stopped uNMN levels returned to normal (149 and 214μg/g Cr respectively). Chromatograms obtained by HPLC-EC clearly showed that amoxicillin co-elutes with uNMN. Patients' uNMN levels measured by LC-MS/MS were in the normal range. Amoxicillin is responsible for analytical interference on HPLC-EC assay for uNMN. This finding can be of help in distinguishing true-positive from false-positive results in the course of a biochemical diagnosis for pheochromocytoma. Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  11. Feocromocitoma asociado a neurofibromatosis de von Recklinghausen Pheochromocytoma associated with von Recklinghausen neurofibromatosis

    Directory of Open Access Journals (Sweden)

    Ramón N. Herrera

    2007-10-01

    Full Text Available El feocromocitoma es un tumor glandular adrenal secretor de hormonas epinefrina y norepinefrina, responsables de regular la frecuencia cardíaca y la presión arterial, entre otras funciones. Este tumor puede ocurrir solo o en combinación con otros desórdenes; los factores genéticos y ambientales juegan un rol clave en su aparición. La neurofibromatosis tipo 1 (NF-1 es un desorden genético frecuente que se hereda en forma autosómica dominante, caracterizado por la formación de neurofibromas (tumores que involucran los nervios tisulares en piel, tejido subcutáneo, nervios craneales y espinales. La NF-1 se diagnostica generalmente con el examen físico. No existe un tratamiento curativo para la NF-1, pero hay modos de tratar algunas de sus complicaciones. La hipertensión arterial en la neurofibromatosis causada por un feocromocitoma es extremadamente rara con una incidencia de menos del 1% en menores de 10 años y en adultos jóvenes. Presentamos el caso clínico de una mujer joven con hipertensión de reciente diagnóstico, con la infrecuente asociación de neurofibromatosis y feocromocitoma. Discutimos los mecanismos fisiopatológicos subyacentes y sus implicancias clínicas.A pheochromo cytoma is an adrenal gland tumor that secretes epinephrine and norepinephrine hormones, and is responsible for regulating heart rate and blood pressure, among other functions. The condition can occur alone or in combination with other disorders, and genetic and environmental factors play a key role. Neurofibromatosis- 1 (NF-1 an inherited "autosomal dominant" disorder is one of the most common genetic disorders, characterized by formation of neurofibromas (tumors involving nerve tissue in the skin, subcutaneous tissue, cranial and spinal root nerves. NF1 generally is diagnosed by physical examination. There is no cure for NF1, but there are ways to treat some of its effects. Neurofibromatosis arterial hypertension caused by pheochromocytoma is extremely

  12. Protective effects of bellidifolin in hypoxia-induced in pheochromocytoma cells (PC12) and underlying mechanisms.

    Science.gov (United States)

    Zhao, Zhi-Ying; Gao, Yang-Yang; Gao, Li; Zhang, Ming; Wang, He; Zhang, Chun-Hong

    2017-01-01

    Bellidifolin, a xanthone compound derived from plants of Gentiana species, is known to exert a variety of pharmacological activities including anti-oxidation, anti-inflammatory and antitumor actions as well as a protective effect on cerebral ischemic nerve injury. The aim of this study was to examine the protective effects of bellidifolin on nerve injury produced by hypoxia and possible underlying mechanisms using pheochromocytoma cells (PC12). Data showed that the viability of PC12 cells subjected to hypoxia resulted in a significant decrease; however; pretreatment with certain concentrations of bellidifolin (20 or 40 μmol/L) prior to hypoxia significantly increased the survival rate. The results of immunohistochemical staining analysis revealed that there were no marked alterations in the expression of pERK protein between all bellidifolin groups while the expression of p-p38MAPK protein was significantly enhanced by hypoxia. Pretreatment with different concentrations of bellidifolin followed by hypoxia significantly decreased the expression of p-p38MAPK protein. The results of western blot analysis showed that hypoxia induced the expression of the MAPK signaling pathway downstream of the key apoptosis factor caspase-3. Compared to hypoxia, the expression of caspase-3 in the presence of belliidifolin was significantly lower. Data suggest that bellidifolin may contribute to the protective effects associated with nerve injury initiated by hypoxia by mechanisms related to inhibition of cell apoptosis independent of the ERK pathway, but may involve blockade of p38MAPK signaling pathway activation and downstream caspase-3 expression.

  13. Feocromocitoma em bovinos de abate: relatos de casos Pheochromocytoma in slaughtered bovine: cases reports

    Directory of Open Access Journals (Sweden)

    W.L.A. Pereira

    2007-04-01

    Full Text Available Relatou-se a ocorrência de dois casos de tumor de medular da adrenal em bovino. O caso 1 foi representado por uma neoplasia de 6,0×4,5cm de tamanho e cor amarelo-acastanhada. O caso 2 constituiu-se de neoplasia maligna, com a lesão primária medindo 33,0×18,0cm e peso de 6,5kg. Metástases estavam presentes nos pulmões e nos linfonodos tráqueobronquiais, mediastínicos e esofagianos. A análise histológica das neoplasias permitiu o diagnóstico de feocromocitoma.Two cases of adrenal medular tumor in bovine are described. In case 1, yellow-brownish neoplasia of 6.0×4.5cm size was observed. Case 2, was constituted of a malignant neoplasia with the primary lesion measuring 33.0×18.0cm and weighing 6.5kg. Metastases were found in the lungs and in the tracheobronchial, mediastinic and oesophageal lymph nodes. Histopathological analysis confirmed the diagnosis of pheochromocytoma.

  14. 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.

  15. G691S/S904S polymorphism in the RET protooncogene of a 25-year-old medical student with bilateral pheochromocytoma

    Science.gov (United States)

    Arneth, Borros

    2009-01-01

    The case of a 25-year-old medical student with bilateral pheochromocytoma is described. Following diagnostic testing, tumors were surgically removed. Genetic analysis revealed that the patient is a heterozygote with the following mutations on opposite homologs: G691S (exon 11) and S904S (TCC-TCG, exon 15), suggesting the diagnosis of multiple endocrine neoplasia 2A (MEN2A). A diagnosis of MEN2 would be an indication of thyroidectomy in this patient. Although this mutation is described in the literature, it has no known connection to pheochromocytomas. Therefore, it is unknown whether there is a causal connection between the G691S genotype and the pheochromocytomas in this patient. If so, G691S is to be added to the list of genotypes causing MEN2A. Here, the procedure of sequencing the RET protooncogene is described and a possible association between the G691S genotype and MEN2A is discussed. PMID:20407648

  16. 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)

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

    Directory of Open Access Journals (Sweden)

    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

  18. Primary diagnosis of multiple pheochromocytomas in the brother of a MEN-2 patient by simultaneous MIBG scintigraphy and low-dose computed tomography

    DEFF Research Database (Denmark)

    Kjaer, Andreas; Petersen, Claus Leth

    2002-01-01

    Metaiodobenzylguanidine (MIBG) scintigraphy is a well-established functional imaging method for localizing pheochromocytomas. However, the morphologic information revealed on the scintigram is often too sparse and thus, accordingly, supplemental computed tomography (CT) or magnetic resonance...... in both adrenal glands and one extra-adrenal pheochromocytoma located in the liver. The combined imaging ensured the final diagnosis without any need for further imaging. Based on the findings of this case, the authors believe that combined MIBG scintigraphy and low-dose CT is a promising future single...

  19. The RET protooncogene in sporadic pheochromocytomas: Frequent multiple endocrine neoplasias type 2 - like mutations and new molecular defects

    Energy Technology Data Exchange (ETDEWEB)

    Beldjord, C.; Desclaux-Arramond, F.; Raffin-Sanson, M. [Universitat Rene Descartes, Paris (France)] [and others

    1994-09-01

    To assess the pathophysiological role of the RET protooncogene in sporadic pheochromocytomas, we examined the two regions of the gene in which molecular defects are specifically associated with the Multiple Endocrine Neoplasias (MEN) type 2A (exons 8-11) and type 2B (exon 16). The sequences of both regions were amplified by RT-PCR or PCR from tumor RNA and/or constitutive DNA. The amplified products were analyzed by denaturing gradient gel electrophoresis using chemical clamps. In 28 patients with unilateral sporadic tumors six RET mutations were found: three in the MEN2A region, and three in the MEN2B region. Five patients had missense mutations: two in the MEN2A region (C634W and D631Y), and three in the MEN2B region (M918T). Analysis of leukocyte DNA in three of these patients confirmed that RET mutations were only present in tumor DNA. The sixth patient had lost exon 10 in the tumor cDNA due to the deletion of the dinucleotide AG at the 3{prime} splice acceptor site of intron 9; this molecular defect was only found in the tumor DNA. Thus RET mutations of the MEN 2A and MEN 2B regions are also found in ca. 20% of sporadic pheochromocytomas. We describe new types of molecular defects of the RET protooncogene in the MEN2A region which involve non-cysteine residues and the loss of exon 10. Further studies should be extended to analyze the entire RET gene. These findings have a profound clinical impact for the management of patients with supposedly sporadic pheochromocytomas.

  20. Targeted Exome Sequencing of Krebs Cycle Genes Reveals Candidate Cancer-Predisposing Mutations in Pheochromocytomas and Paragangliomas.

    Science.gov (United States)

    Remacha, Laura; Comino-Méndez, Iñaki; Richter, Susan; Contreras, Laura; Currás-Freixes, María; Pita, Guillermo; Letón, Rocío; Galarreta, Antonio; Torres-Pérez, Rafael; Honrado, Emiliano; Jiménez, Scherezade; Maestre, Lorena; Moran, Sebastian; Esteller, Manel; Satrústegui, Jorgina; Eisenhofer, Graeme; Robledo, Mercedes; Cascón, Alberto

    2017-10-15

    Purpose: Mutations in Krebs cycle genes are frequently found in patients with pheochromocytomas/paragangliomas. Disruption of SDH, FH or MDH2 enzymatic activities lead to accumulation of specific metabolites, which give rise to epigenetic changes in the genome that cause a characteristic hypermethylated phenotype. Tumors showing this phenotype, but no alterations in the known predisposing genes, could harbor mutations in other Krebs cycle genes. Experimental Design: We used downregulation and methylation of RBP1, as a marker of a hypermethylation phenotype, to select eleven pheochromocytomas and paragangliomas for targeted exome sequencing of a panel of Krebs cycle-related genes. Methylation profiling, metabolite assessment and additional analyses were also performed in selected cases. Results: One of the 11 tumors was found to carry a known cancer-predisposing somatic mutation in IDH1 A variant in GOT2 , c.357A>T, found in a patient with multiple tumors, was associated with higher tumor mRNA and protein expression levels, increased GOT2 enzymatic activity in lymphoblastic cells, and altered metabolite ratios both in tumors and in GOT2 knockdown HeLa cells transfected with the variant. Array methylation-based analysis uncovered a somatic epigenetic mutation in SDHC in a patient with multiple pheochromocytomas and a gastrointestinal stromal tumor. Finally, a truncating germline IDH3B mutation was found in a patient with a single paraganglioma showing an altered α-ketoglutarate/isocitrate ratio. Conclusions: This study further attests to the relevance of the Krebs cycle in the development of PCC and PGL, and points to a potential role of other metabolic enzymes involved in metabolite exchange between mitochondria and cytosol. Clin Cancer Res; 23(20); 6315-24. ©2017 AACR . ©2017 American Association for Cancer Research.

  1. Rapid clearance of iodine-131 MIBG from the heart and liver of patients with adrenergic dysfunction and pheochromocytoma

    International Nuclear Information System (INIS)

    Nakajo, M.; Shimabukuro, K.; Miyaji, N.; Shimada, J.; Shirono, K.; Sakata, H.; Yoshimura, H.; Yonekura, R.; Shinohara, S.

    1985-01-01

    Iodine-131 MIBG, a radiolabeled adrenergic neuron-blocking agent, decreased rapidly from the heart and liver of patients with adrenergic dysfunction and pheochromocytoma when compared with eight controls. However, there was no significant difference in the rate of [ 131 I]MIBG decrease in these organs between controls and patients in the intervals subsequent to 4 hr. These findings suggest that adrenergic neuronal uptake of [ 131 I]MIBG in these organs is smaller in the patients than in the controls. Measurements of time-activity relationships of radioiodinated MIBG may be useful for assessment of adrenergic function of these organs and thus of generalized disorders of adrenergic innervation

  2. Plasma beta-endorphins and catecholamines before and after clonidine in essential hypertension and pheochromocytoma.

    Science.gov (United States)

    Chodakowska, J; Wocial, B; Januszewicz, W; Chojnowski, K; Feltynowski, T; Lazecki, D

    1987-01-01

    To investigate the possible release of beta-endorphins (beta EN) from tumors and to investigate their possible involvement in the hypotensive mechanism of clonidine (CLO) in pheochromocytoma (PHEO), as compared with essential hypertension (EH), we studied 12 patients with PHEO, 17 patients with uncomplicated stable EH (SEH), nine patients with borderline EH (BEH), and seven healthy volunteers (N). All subjects were hospitalized and excreted normal amounts of sodium. Mean blood pressure (MAP) and plasma beta EN, norepinephrine (NE), epinephrine (E), and dopamine (DA) were measured before and 180 min after an oral dose of 0.3 mg CLO. Following CLO, a significant (p less than 0.01) decrease in MAP was present in all groups. Plasma NE and E decreased (p less than 0.02 to p less than 0.01) in N, BEH, and SEH, but not in PHEO. DA did not change in any group. Pretreatment beta EN did not differ significantly between the groups, and following CLO it did not change in N or PHEO, while it increased significantly in BEH (p less than 0.01) and in SEH (p less than 0.02). Absolute changes in MAP correlated with those of beta EN only in the SEH group. Changes in NE or E did not correlate with changes in MAP in either group. Likewise, changes in NE or E were not correlated with those of beta EN, in N or EH, but a correlation between resting plasma E and resting beta EN concentrations was demonstrated in PHEO. These results support a role of beta EN in the hypotensive action of CLO in EH, but not in N or PHEO.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Efficacy of Peptide Receptor Radionuclide Therapy for Functional Metastatic Paraganglioma and Pheochromocytoma.

    Science.gov (United States)

    Kong, Grace; Grozinsky-Glasberg, Simona; Hofman, Michael S; Callahan, Jason; Meirovitz, Amichay; Maimon, Ofra; Pattison, David A; Gross, David J; Hicks, Rodney J

    2017-09-01

    Treatment options for unresectable paraganglioma (PGL)/pheochromocytoma (PCC), especially with uncontrolled secondary hypertension (HTN), are limited. Preliminary studies with peptide receptor radionuclide therapy (PRRT) suggest efficacy, but data on HTN control and survival are lacking. We assessed PRRT outcomes in such patients from two referral centers. Twenty consecutive patients (13 men; age range, 21 to 77 years) with high somatostatin receptor (SSTR) expression treated with 177Lu-DOTA-octreotate, nine with radiosensitizing chemotherapy, were retrospectively reviewed. Median cumulative activity was 22 GBq (median 4 cycles). Fourteen patients were treated for uncontrolled HTN and six for progressive or symptomatic metastatic disease or local recurrence. Three months after PRRT, 8 of 14 patients treated for HTN required reduced medication doses, 5 had no change in anti-HTN doses, and 1 was lost to follow-up. Eighty-six percent had serum chromogranin-A reduction. Of the entire cohort, 36% had disease regression (29% partial and 7% minor response) on computed tomography, with stable findings in 50%. Three other patients had bony disease evaluable only on SSTR imaging (2 partial response and 1 stable). Median progression-free survival was 39 months; median overall survival was not reached (5 deaths; median follow-up, 28 months). Four patients had grade 3 lymphopenia; 2 had grade 3 thrombocytopenia. Renal impairment in 2 patients was attributed to underlying disease processes. PRRT achieves worthwhile clinical and biochemical responses with low toxicity and encouraging survival in PGL/PCC. Because PRRT has logistic and radiation-safety advantages compared to 131I-MIBG therapy, further prospective evaluation is warranted. Copyright © 2017 Endocrine Society

  4. Sdhd and SDHD/H19 knockout mice do not develop paraganglioma or pheochromocytoma.

    Directory of Open Access Journals (Sweden)

    Jean-Pierre Bayley

    Full Text Available BACKGROUND: Mitochondrial succinate dehydrogenase (SDH is a component of both the tricarboxylic acid cycle and the electron transport chain. Mutations of SDHD, the first protein of intermediary metabolism shown to be involved in tumorigenesis, lead to the human tumors paraganglioma (PGL and pheochromocytoma (PC. SDHD is remarkable in showing an 'imprinted' tumor suppressor phenotype. Mutations of SDHD show a very high penetrance in man and we postulated that knockout of Sdhd would lead to the development of PGL/PC, probably in aged mice. METHODOLOGY/PRINCIPAL FINDINGS: We generated a conventional knockout of Sdhd in the mouse, removing the entire third exon. We also crossed this mouse with a knockout of H19, a postulated imprinted modifier gene of Sdhd tumorigenesis, to evaluate if loss of these genes together would lead to the initiation or enhancement of tumor development. Homozygous knockout of Sdhd results in embryonic lethality. No paraganglioma or other tumor development was seen in Sdhd KO mice followed for their entire lifespan, in sharp contrast to the highly penetrant phenotype in humans. Heterozygous Sdhd KO mice did not show hyperplasia of paraganglioma-related tissues such as the carotid body or of the adrenal medulla, or any genotype-related pathology, with similar body and organ weights to wildtype mice. A cohort of Sdhd/H19 KO mice developed several cases of profound cardiac hypertrophy, but showed no evidence of PGL/PC. CONCLUSIONS: Knockout of Sdhd in the mouse does not result in a disease phenotype. H19 may not be an initiator of PGL/PC tumorigenesis.

  5. 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

  6. 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.

  7. Phase II trial of pazopanib in advanced/progressive malignant pheochromocytoma and paraganglioma.

    Science.gov (United States)

    Jasim, Sina; Suman, Vera J; Jimenez, Camilo; Harris, Pamela; Sideras, Kostandinos; Burton, Jill K; Worden, Francis Paul; Auchus, Richard J; Bible, Keith C

    2017-08-01

    Pheochromocytomas and paragangliomas (Pheo/PGL) are rare, vascular, sometimes malignant endocrine tumors. Case reports indicate the activity of vascular endothelium growth factor receptor-targeted kinase inhibitors in these cancers. To assess the antitumor activity and tolerability of pazopanib in progressive malignant Pheo/PGL. This multicenter Phase II trial (MC107C) enrolled individuals  ≥18 years old with disease progression ≤ 6 months prior to registration, Eastern Cooperative Oncology Group PS 0-2, and measurable disease (response evaluation criteria in solid tumors 1.0). Pazopanib was administered in 28-day cycles, with the regimen ultimately being as follows: cycle 1: 400 mg daily on days 1-14, cycle 2: 800 mg daily on days 1-14, and then cycle 2 + : 800 mg daily on all days. The study was halted due to poor accrual. Seven patients were enrolled (05/2011-11/2014). One patient withdrew consent prior to treatment, leaving six evaluable patients. Treatment was discontinued, due to the following reasons: disease progression (4); withdrawal (1); and grade 4 (Takotsubo) cardiomyopathy (1). The median number of cycles administered was 4 (range: 2-29, total: 49). Four patients had >1 dose reduction due to the following reasons: fatigue (1), abnormal liver tests (2), hypertension and (Takotsubo) cardiomyopathy (1), and headaches (1). Common severe (Common Terminology Criteria for Adverse Events v3.0 grades 3-5) toxicities were as follows: hypertension (3/6), (Takotsubo) cardiomyopathy (2/6), diarrhea (1/6), fatigue (1/6), headache (1/6), and hematuria (1/6). One confirmed partial response was observed in PGL (17%, duration 2.4 years); median progression-free survival and overall survival were 6.5 and 14.8 months, respectively. Pazopanib has activity in Pheo/PGL requiring more study; optimal alpha- and beta-blockade are imperative pre-therapy in patients with secretory tumors, as risk of hypertension and cardiomyopathy are potentially life

  8. Diagnosis of pheochromocytoma using (123I)-compared with (131I)-metaiodobenzylguanidine scintigraphy

    International Nuclear Information System (INIS)

    Furuta, Nozomu; Kiyota, Hiroshi; Yoshigoe, Fukuo; Hasegawa, Norio; Ohishi, Yukihiko

    1999-01-01

    Patient with pheochromocytoma (PCT) cannot be cured without operation, therefore, preoperative determination of the localization of PCT should be performed accurately. ( 131 I)-Metaiodobenzylguanidine (MIBG) scintigraphy is a gold standard for the diagnosis of PCT. However, ( 123 I)-MIBG is also found to accumulate in PCT. In order to clarify the usefulness of ( 123 I)-MIBG scintigraphy for the local detection of PCT, we compared the distribution of ( 123 I)- and ( 131 I)-MIBG in patients with or without PCT. ( 131 I)- and ( 123 I)-MIBG scintigraphy was performed in 29 and 16 patients, respectively. In the former group, 14 patients had PCT, 12 had hypertension without any adrenal disorder and three had other diseases. In the latter group, eight patients had PCT, two had hypertension without any adrenal disorder and six had other diseases. The sensitivity, specificity and accuracy of ( 123 I)- with ( 131 I)-MIBG scintigraphy were compared. The sensitivity of ( 131 I)- and ( 123 I)-MIBG scintigraphy was 85.7 and 90%, respectively. The specificity of each test was 100%. The accuracy of ( 131 I)- and ( 123 I)-MIBG scintigraphy was 93.1 and 95%, respectively. The quality of images obtained using ( 123 I)-MIBG was better than with ( 131 I)-MIBG, because ( 123 I)-MIBG generated a higher dose of γ-rays with a higher specificity than ( 131 I)-MIBG. In addition, normal adrenal grands were visualized in 50% of patients tested with ( 123 I)-MIBG scintigraphy. These results indicate that ( 123 I)-MIBG scintigraphy is a valuable tool for the local detection of PCT, as is ( 131 I)-MIBG scintigraphy. Furthermore, it is possible that ( 123 I)-MIBG can be used as an alternative to ( 131 I)-MIBG for the detection of PCT. Our study was not a prospective study and the background of the patients was not matched. Further prospective studies are needed in order to determine the efficacy of ( 123 I)-MIBG scintigraphy for the diagnosis of PCT. (author)

  9. 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

  10. Clinical and Molecular Features of Renal and Pheochromocytoma/Paraganglioma Tumor Association Syndrome (RAPTAS): Case Series and Literature Review.

    Science.gov (United States)

    Casey, Ruth T; Warren, Anne Y; Martin, Jose Ezequiel; Challis, Benjamin G; Rattenberry, Eleanor; Whitworth, James; Andrews, Katrina A; Roberts, Thomas; Clark, Graeme R; West, Hannah; Smith, Philip S; Docquier, France M; Rodger, Fay; Murray, Vicki; Simpson, Helen L; Wallis, Yvonne; Giger, Olivier; Tran, Maxine; Tomkins, Susan; Stewart, Grant D; Park, Soo-Mi; Woodward, Emma R; Maher, Eamonn R

    2017-11-01

    The co-occurrence of pheochromocytoma (PC) and renal tumors was linked to the inherited familial cancer syndrome von Hippel-Lindau (VHL) disease more than six decades ago. Subsequently, other shared genetic causes of predisposition to renal tumors and to PC, paraganglioma (PGL), or head and neck paraganglioma (HNPGL) have been described, but case series of non-VHL-related cases of renal tumor and pheochromocytoma/paraganglioma tumor association syndrome (RAPTAS) are rare. To determine the clinical and molecular features of non-VHL RAPTAS by literature review and characterization of a case series. A review of the literature was performed and a retrospective study of referrals for investigation of genetic causes of RAPTAS. Literature review revealed evidence of an association, in addition to VHL disease, between germline mutations in SDHB, SDHC, SDHD, TMEM127, and MAX genes and RAPTAS [defined here as the co-occurrence of tumors from both classes (PC/PGL/HNPGL and renal tumors) in the same individual or in first-degree relatives]. In both the literature review and our case series of 22 probands with non-VHL RAPTAS, SDHB mutations were the most frequent cause of non-VHL RAPTAS. A genetic cause was identified in 36.3% (8/22) of kindreds. Renal tumors and PC/PGL/HNPGL tumors share common molecular features and their co-occurrence in an individual or family should prompt genetic investigations. We report a case of MAX-associated renal cell carcinoma and confirm the role of TMEM127 mutations with renal cell carcinoma predisposition. Copyright © 2017 Endocrine Society

  11. 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.

  12. Phosphodiesterase 2 negatively regulates adenosine-induced transcription of the tyrosine hydroxylase gene in PC12 rat pheochromocytoma cells.

    Science.gov (United States)

    Makuch, Edyta; Kuropatwa, Marianna; Kurowska, Ewa; Ciekot, Jaroslaw; Klopotowska, Dagmara; Matuszyk, Janusz

    2014-07-05

    Adenosine induces expression of the tyrosine hydroxylase (TH) gene in PC12 cells. However, it is suggested that atrial natriuretic peptide (ANP) inhibits expression of this gene. Using real-time PCR and luciferase reporter assays we found that ANP significantly decreases the adenosine-induced transcription of the TH gene. Results of measurements of cyclic nucleotide concentrations indicated that ANP-induced accumulation of cGMP inhibits the adenosine-induced increase in cAMP level. Using selective phosphodiesterase 2 (PDE2) inhibitors and a synthetic cGMP analog activating PDE2, we found that PDE2 is involved in coupling the ANP-triggered signal to the cAMP metabolism. We have established that ANP-induced elevated levels of cGMP as well as cGMP analog stimulate hydrolytic activity of PDE2, leading to inhibition of adenosine-induced transcription of the TH gene. We conclude that ANP mediates negative regulation of TH gene expression via stimulation of PDE2-dependent cAMP breakdown in PC12 cells. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  13. A diagnosis pitfall: the cystic bilateral pheochromocytoma. Discussion of a case; Un piege diagnostique: le pheocromocytome bilateral kystique. A propos d`un cas

    Energy Technology Data Exchange (ETDEWEB)

    Devillers, A.; Bedig, G.; Garin, E.; Bouyaux, M.; Lecloirec, J. [CHG St Brieuc CRLCC Eugene Marquis Rennes (France)

    1997-12-31

    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 {mu} 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-{sup 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 {sup 131}I must be part in the examination for suspicion of pheochromocytoma and must be interpreted together with the TDM morphological data

  14. 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.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

  20. Meta[{sup 131}I]iodobenzylguanidine therapy for patients with metastatic and unresectable pheochromocytoma and paraganglioma

    Energy Technology Data Exchange (ETDEWEB)

    Goldsby, Robert E. [Division of Pediatric Oncology, Department of Pediatrics, University of California, San Francisco, CA 94143-0106 (United States); Fitzgerald, Paul A. [Division of Endocrinology, Department of Medicine, University of California, San Francisco, CA 94143-1222 (United States)], E-mail: paul.fitzgerald@ucsf.edu

    2008-08-15

    Introduction: Pheochromocytomas (PHEOs) and paragangliomas (PGLs) are tumors that can exhibit a malignant behavior. Targeted radiotherapy with {sup 131}I-metaiodobenzylguanidine ({sup 131}I-MIBG) has proven useful in patients with unresectable, metastatic and/or relapsed disease. Methods: We review the literature and our experience at UCSF to highlight important characteristics of PHEO/PGL and the use of {sup 131}I-MIBG in the treatment of this disease. Results: These tumors are rare, with a diagnosed incidence of only two to four cases per million annually; 40% are discovered at autopsy. Clinical manifestations are caused by excess secretion of catecholamines, although some PGLs are nonsecretory. Approximately 25% of patients with PHEO/PGLs have an underlying genetic predisposition. The risk of a germline mutation is higher in children. Diagnostic evaluation should include serial determinations of fractionated metanephrines and serum chromogranin A. Staging requires both {sup 123}I-MIBG and full-body magnetic resonance imaging or {sup 18}FDG-PET scanning. The primary treatment for PHEO/PGL is resection. Patients may be candidates for treatment with {sup 131}I-MIBG if they have unresectable or metastatic tumors that are avid for MIBG. Such patients usually respond to this targeted radioisotope therapy and many achieve a durable remission. Myelosuppression is a dose-related side effect that can be treated with transfusions or autologous hematopoietic stem cells. Late side effects can include infertility, myelodysplasia and second cancers. Conclusions: Treatment with {sup 131}I-MIBG can be considered for patients if surgery is not feasible. There are significant risks associated with this treatment, but the majority of patients will respond. Treatment with {sup 131}I-MIBG should be done at institutions with experience in delivering targeted radiotherapeutics.

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

    Science.gov (United States)

    Richter, Susan; Peitzsch, Mirko; Rapizzi, Elena; Lenders, Jacques W; Qin, Nan; de Cubas, Aguirre A; Schiavi, Francesca; Rao, Jyotsna U; Beuschlein, Felix; Quinkler, Marcus; Timmers, Henri J; Opocher, Giuseppe; Mannelli, Massimo; Pacak, Karel; Robledo, Mercedes; Eisenhofer, Graeme

    2014-10-01

    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. We assessed whether altered succinate dehydrogenase product-precursor relationships, manifested by differences in tumor ratios of succinate to fumarate or other metabolites, might aid in identifying and stratifying patients with SDHx mutations. PPGL tumor specimens from 233 patients, including 45 with SDHx mutations, were provided from eight tertiary referral centers for mass spectrometric analyses of Krebs cycle metabolites. Diagnostic performance of the succinate:fumarate ratio for identification of pathogenic SDHx mutations. SDH-deficient PPGLs were characterized by 25-fold higher succinate and 80% lower fumarate, cis-aconitate, and isocitrate tissue levels than PPGLs without SDHx mutations. Receiver-operating characteristic curves for use of ratios of succinate to fumarate or to cis-aconitate and isocitrate to identify SDHx mutations indicated areas under curves of 0.94 to 0.96; an optimal cut-off of 97.7 for the succinate:fumarate ratio provided a diagnostic sensitivity of 93% at a specificity of 97% to identify SDHX-mutated PPGLs. Succinate:fumarate ratios were higher in both SDHB-mutated and metastatic tumors than in those due to SDHD/C mutations or without metastases. Mass spectrometric-based measurements of ratios of succinate:fumarate and other metabolites in PPGLs offer a useful method to identify patients for testing of SDHx mutations, with additional utility to quantitatively assess functionality of mutations and metabolic factors responsible for malignant risk.

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

    Energy Technology Data Exchange (ETDEWEB)

    Neet, K.E.; Kasaian, M.

    1987-05-01

    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 SVI-NGF was bound to rat PC12 cells in suspension for 30 min at 37, 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 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. 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.

  3. 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

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  6. 18F-fluorodihydroxyphenylalanine PET/CT in pheochromocytoma and paraganglioma: relation to genotype and amino acid transport system L

    International Nuclear Information System (INIS)

    Feral, Chloe C.; Tissot, Floriane S.; Tosello, Lionel; Fakhry, Nicolas; Sebag, Frederic; Pacak, Karel; Taieb, David

    2017-01-01

    F-FDOPA is a highly sensitive and specific radiopharmaceutical for pheochromocytoma and paraganglioma (PPGL) imaging. However, 18 F-FDOPA might be falsely negative in these tumors, especially those related to mutations in succinate dehydrogenase genes (SDHx). The aim of the present study was to evaluate the relationship between expression of L-DOPA transporters and 18 F-FDOPA PET imaging results in PPGL. From 2007 to 2015, 175 patients with non-metastatic PPGL were evaluated by 18 F-FDOPA PET/CT for initial diagnosis/staging and follow-up. 18 F-FDOPA PET/CT was considered as falsely negative for at least one lesion in 10/126 (8%) patients (two sporadic, six SDHD, two SDHB PPGLs). The mRNA and protein expression levels of CD98hc and LATs were evaluated in samples with different genetic backgrounds and imaging phenotypes. The qRT-PCR and immunohistochemical analyses were performed in 14 and 16 tumor samples, respectively. The SDHx mutated samples exhibited a significant decrease in mRNA expression of LAT3 when compared to sporadic PPGLs (P = 0.042). There was also a statistical trend toward decreased CD98hc (P = 0.147) and LAT4 (P = 0.012) levels in SDHx vs sporadic PPGLs. No difference was observed for LAT1/LAT2 mRNA levels. LAT1 protein was expressed in 15 out of 16 (93.75%) SDHx tumors, regardless of the 18 F-FDOPA positivity. LAT1 and CD98hc were co-expressed in 6/8 18 F-FDOPA-negative PPGLs. In contrast, in one case with absence of LAT1/CD98hc, 18 F-FDOPA uptake was positive and attributed to LAT4 expression. We conclude that down-regulation of LAT1/CD98hc cannot explain the imaging phenotype of SDHx-related PPGLs. A reduced activity of LAT1 remains the primary hypothesis possibly due to a modification of intracellular amino acid content which may reduce 18 F-FDOPA uptake. (orig.)

  7. ROS production is essential for the apoptotic function of E2F1 in pheochromocytoma and neuroblastoma cell lines.

    Directory of Open Access Journals (Sweden)

    Lilia Espada

    Full Text Available In this study we demonstrate that accumulation of reactive oxygen species (ROS is essential for E2F1 mediated apoptosis in ER-E2F1 PC12 pheochromocytoma, and SH-SY5Y and SK-N-JD neuroblastoma stable cell lines. In these cells, the ER-E2F1 fusion protein is expressed in the cytosol; the addition of 4-hydroxytamoxifen (OHT induces its translocation to the nucleus and activation of E2F1target genes. Previously we demonstrated that, in ER-E2F1 PC12 cells, OHT treatment induced apoptosis through activation of caspase-3. Here we show that caspase-8 activity did not change upon treatment with OHT. Moreover, over-expression of Bcl-xL arrested OHT-induced apoptosis; by contrast, over-expression of c-FLIP, did not have any effect on OHT-induced apoptosis. OHT addition induces BimL expression, its translocation to mitochondria and activation of Bax, which is paralleled by diminished mitochondrial enrichment of Bcl-xL. Treatment with a Bax-inhibitory peptide reduced OHT-induced apoptosis. These results point out the essential role of mitochondria on the apoptotic process driven by E2F1. ROS accumulation followed E2F1 induction and treatment with the antioxidant N-acetylcysteine, inhibited E2F1-induced Bax translocation to mitochondria and subsequent apoptosis. The role of ROS in mediating OHT-induced apoptosis was also studied in two neuroblastoma cell lines, SH-SY5Y and SK-N-JD. In SH-SY5Y cells, activation of E2F1 by the addition of OHT induced ROS production and apoptosis, whereas over-expression of E2F1 in SK-N-JD cells failed to induce either response. Transcriptional profiling revealed that many of the genes responsible for scavenging ROS were down-regulated following E2F1-induction in SH-SY5Y, but not in SK-N-JD cells. Finally, inhibition of GSK3β blocked ROS production, Bax activation and the down regulation of ROS scavenging genes. These findings provide an explanation for the apparent contradictory role of E2F1 as an apoptotic agent versus a cell

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

    Directory of Open Access Journals (Sweden)

    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

  9. Nongenomic mechanisms of physiological estrogen-mediated dopamine efflux

    Directory of Open Access Journals (Sweden)

    Watson Cheryl S

    2009-06-01

    Full Text Available Abstract Background Neurological diseases and neuropsychiatric disorders that vary depending on female life stages suggest that sex hormones may influence the function of neurotransmitter regulatory machinery such as the dopamine transporter (DAT. Results In this study we tested the rapid nongenomic effects of several physiological estrogens [estradiol (E2, estrone (E1, and estriol (E3] on dopamine efflux via the DAT in a non-transfected, NGF-differentiated, rat pheochromocytoma (PC12 cell model that expresses membrane estrogen receptors (ERs α, β, and GPR30. We examined kinase, ionic, and physical interaction mechanisms involved in estrogenic regulation of the DAT function. E2-mediated dopamine efflux is DAT-specific and not dependent on extracellular Ca2+-mediated exocytotic release from vesicular monoamine transporter vesicles (VMATs. Using kinase inhibitors we also showed that E2-mediated dopamine efflux is dependent on protein kinase C and MEK activation, but not on PI3K or protein kinase A. In plasma membrane there are ligand-independent associations of ERα and ERβ (but not GPR30 with DAT. Conditions which cause efflux (a 9 min 10-9 M E2 treatment cause trafficking of ERα (stimulatory to the plasma membrane and trafficking of ERβ (inhibitory away from the plasma membrane. In contrast, E1 and E3 can inhibit efflux with a nonmonotonic dose pattern, and cause DAT to leave the plasma membrane. Conclusion Such mechanisms explain how gender biases in some DAT-dependent diseases can occur.

  10. Staging and Functional Characterization of Pheochromocytoma and Paraganglioma by 18F-Fluorodeoxyglucose (18F-FDG) Positron Emission Tomography

    Science.gov (United States)

    Timmers, Henri J. L. M.; Chen, Clara C.; Carrasquillo, Jorge A.; Whatley, Millie; Ling, Alexander; Eisenhofer, Graeme; King, Kathryn S.; Rao, Jyotsna U.; Wesley, Robert A.; Adams, Karen T.

    2012-01-01

    Background Pheochromocytomas and paragangliomas (PPGLs) are rare tumors of the adrenal medulla and extra-adrenal sympathetic chromaffin tissues; their anatomical and functional imaging are critical to guiding treatment decisions. This study aimed to compare the sensitivity and specificity of 18F-fluorodeoxyglucose positron emission tomography with computed tomography (18F-FDG PET/CT) for tumor localization and staging of PPGLs with that of conventional imaging by [123I]-metaiodobenzylguanidine single photon emission CT (123I-MIBG SPECT), CT, and magnetic resonance imaging (MRI). Methods A total of 216 patients (106 men, 110 women, aged 45.2 ± 14.9 years) with suspected PPGL underwent CT or MRI, 18F-FDG PET/CT, and 123I-MIBG SPECT/CT. Sensitivity and specificity were measured as endpoints and compared by the McNemar test, using two-sided P values only. Results Sixty (28%) of patients had nonmetastatic PPGL, 95 (44%) had metastatic PPGL, and 61 (28%) were PPGL negative. For nonmetastatic tumors, the sensitivity of 18F-FDG was similar to that of 123I-MIBG but less than that of CT/MRI (sensitivity of 18F-FDG = 76.8%; of 123I-MIBG = 75.0%; of CT/MRI = 95.7%; 18F-FDG vs 123I-MIBG: difference = 1.8%, 95% confidence interval [CI] = −14.8% to 14.8%, P = .210; 18F-FDG vs CT/MRI: difference = 18.9%, 95% CI = 9.4% to 28.3%, P < .001). The specificity was 90.2% for 18F-FDG, 91.8% for 123I-MIBG, and 90.2% for CT/MRI. 18F-FDG uptake was higher in succinate dehydrogenase complex– and von Hippel–Lindau syndrome–related tumors than in multiple endocrine neoplasia type 2 (MEN2) related tumors. For metastases, sensitivity was greater for 18F-FDG and CT/MRI than for 123I-MIBG (sensitivity of 18F-FDG = 82.5%; of 123I-MIBG = 50.0%; of CT/MRI = 74.4%; 18F-FDG vs 123I-MIBG: difference = 32.5%, 95% CI = 22.3% to 42.5%, P < .001; CT/MRI vs 123I-MIBG: difference = 24.4%, 95% CI = 11.3% to 31.6%, P < .001). For bone metastases, 18F-FDG was more sensitive than CT/MRI (sensitivity of 18

  11. The Epidemiology of Pheochromocytoma

    DEFF Research Database (Denmark)

    Ebbehoj, A; Søndergaard, Esben; Trolle, Christian

    for all patients in the Northern and Central Regions of Denmark. Incidence rates were calculated using Poisson regression and time trends were analysed with year as a continuous explanatory variable. Results:  We found an increasing trend from 2.06 (CI95% 1.68-2.49) per million person-years 1977-2006 to 4...

  12. The Epidemiology of Pheochromocytoma

    DEFF Research Database (Denmark)

    Ladefoged Ebbehøj, Andreas

    2017-01-01

    evaluation of health records. IR was calculated using Poisson regression and time trends were analysed with year as a continuous explanatory variable. Validity of diagnosis codes was expressed in positive predictive values (PPV). We found a highly significant increase in IR (p

  13. ACTH-producing pheochromocytoma.

    Science.gov (United States)

    Berenyi, M R; Singh, G; Gloster, E S; Davidson, M I; Woldenberg, D H

    1977-01-01

    A benign adrenal medullary tumor that secreted adrenocorticotropic hormone (ACTH) was associated with bilateral adrenocortical hyperplasia and clinically evident Cushing syndrome. The clinical and chemical features were those usually associated with pituitary Cushing disease, including partial suppression of urinary OH steroids after administration of 8 mg of dexamethasone. The fractionization of the tumor's ACTH revealed 70% little "biologically active" ACTH, which is usually found in this concentration only in pituitary tissue.

  14. Pheochromocytoma and Paraganglioma

    Science.gov (United States)

    ... Español NICHD Theme Browse AZTopics Browse A-Z Adrenal Gland Disorders Autism Spectrum Disorder (ASD) Down Syndrome Endometriosis Learning ... Funding Opportunities & Notices Health A to Z List Adrenal Gland Disorders About NICHD Research Information Find a Study More ...

  15. Comparative toxicity and carcinogenicity studies of tetracycline and oxytetracycline in rats and mice.

    Science.gov (United States)

    Dietz, D D; Abdo, K M; Haseman, J K; Eustis, S L; Huff, J E

    1991-08-01

    Two-year toxicity and carcinogenicity studies of oxytetracycline hydrochloride and tetracycline hydrochloride, two structurally similar and widely used antibiotics, were performed in F344/N rats and B6C3F1 mice. Rats and mice were continuously exposed via their diet to the following levels of antibiotic: oxytetracycline HCl--rats 0, 25,000, or 50,000 ppm; mice 0,6,300, or 12,500 ppm; tetracycline HCl--rats and mice 0, 12,500, or 25,000 ppm. On a milligram per kilogram of body weight basis these exposures represent doses that are 20 to 140 times daily human therapeutic doses. Dose-related increased survival was noted among oxytetracycline-treated male rats and tetracycline-treated female rats and male mice, while treatment-related reduced body weight gain occurred in oxytetracycline- and tetracycline-treated mice. Microscopic changes included fatty metamorphosis and focal cellular change in livers of oxytetracycline-treated male rats and basophilic cytoplasmic and clear cell change in livers of tetracycline-treated male rats. The only neoplastic changes were a marginally increased trend in pheochromocytoma of the adrenal medulla (equivocal evidence only) among oxytetracycline-exposed male rats (12/50 controls, 19/50 low dose, 24/50 high dose) and an increased incidence of pituitary adenoma or adenocarcinoma among high-dose oxytetracycline-treated female rats (20/50 controls, 32/50 high dose). Although oxytetracycline and tetracycline appeared to increase the incidence of pituitary hyperplasia in high-dose male and female rats, respectively, the total incidence of proliferative changes (hyperplasia, adenoma, and adenocarcinoma) was not affected by antibiotic exposure. The results from these studies therefore support the notion that neither antibiotic is carcinogenic in rodents. There were several negative trends suggesting possible protective effects by both these tetracycline analogs against certain spontaneous neoplastic and non-neoplastic changes.

  16. Characterization of alpha-latrotoxin interaction with rat brain synaptosomes and PC12 cells.

    Science.gov (United States)

    Grasso, A; Pelliccia, M; Alemà, S

    1982-01-01

    alpha-latrotoxin, a polypeptide neurotoxin purified from the venom of the spider Latrodectus mactans tredecimguttatus, induces a massive release of a variety of neurotransmitters from rat brain synaptosomes and a clonal pheochromocytoma cell line (PC12 cells). In both systems secretion of catecholamines is dose- and calcium-dependent. Efflux of catecholamines is coupled with a substantial release of intracellular ATP. Independent of alpha-latrotoxin with PC12 cells is followed by a rapid influx of calcium and sodium ions, the rate being dependent on toxin and calcium concentrations. By reductive methylation it is possible to radioactively label alpha-latrotoxin without appreciable loss of neurotoxicity. A sensitive binding assay in vitro allows the identification of a limited number of specific binding sites in central nervous system synaptic membranes and PC12 cells, for which tritiated alpha-latrotoxin displays nanomolar affinity.

  17. Comparative Study on the Protective Effects of Salidroside and Hypoxic Preconditioning for Attenuating Anoxia-Induced Apoptosis in Pheochromocytoma (PC12) Cells.

    Science.gov (United States)

    Hu, Yao; Lv, Xiumei; Zhang, Jing; Meng, Xianli

    2016-10-30

    BACKGROUND Hypoxia is an important sign that can result from body injuries or a special condition such as being at a high altitude or deep water diving. In the current studies, hypoxic preconditioning (HPC) plays a key role in reducing hypoxia-induced apoptosis. We aimed to study the pharmacologic preconditioning effects of salidroside versus those of HPC in hypoxia-/anoxia-induced apoptosis in PC12 cells (pheochromocytoma). MATERIAL AND METHODS PC12 cells were treated by different experimental conditions: control condition, hypoxia condition, HPC condition, low-/middle-/high-dose condition of salidroside, cyclosporine A (CsA), and oratractyloside (ATR). The cell viability, lactate dehydrogenase (LDH) activity, apoptosis, mitochondrial membrane potential (MMP), intracellular Ca2+, caspase-3 activity, and expression of Bcl-2 were detected in PC12 cells after the hypoxia treatment. Salidroside, extracted from the traditional Chinese herb Rhodiola rosea L, plays an essential role in reducing hypoxia-induced apoptosis in PC12 cells by the mitochondrial pathway. RESULTS Salidroside decreased the apoptosis and increased the viability of hypoxia-induced PC12 cells more effectively than HPC Moreover, salidroside markedly stabilized MMP and intracellular Ca2+, reduced or inhibited LDH and caspase-3 activity, and up-regulated Bcl-2; CsA and ATR showed corresponding function. CONCLUSIONS Salidroside administration restrains apoptosis induced by hypoxia in PC12 cells. The protective effects are mediated by preservation of mitochondrial integrity and MMP to inhibit the excessive Ca2+ influx and caspase-3 activity and to promote the Bcl-2 expression, providing a potential clinical and effective therapeutic mechanism to reduce deaths from ischemic or hypoxic injury.

  18. Bicyclic monoterpene diols induce differentiation of S91 melanoma and PC12 pheochromocytoma cells by a cyclic guanosine-monophosphate-dependent pathway.

    Science.gov (United States)

    Brown, D A; Lesiak, K; Ren, W Y; Strzelecki, K L; Khorlin, A A

    1999-02-01

    Previously, we showed that 5-norbornene-2,2-dimethanol (5-NBene-2,2-DM) is an effective inducer of melanogenesis in cultured cells and guinea-pig skin [Brown et al. (1998) J. Invest. Dermatol., 110:428-437]. This study shows that 2,3-cis/exo-pinanediol (2,3-cs/ex-PinD) is a more effective inducer of melanogenesis than 5-NBene-2,2-DM in S91 mouse melanoma cells. Furthermore, 2,3-cs/ex-PinD appears to penetrate guinea-pig skin better than 5-NBene-2,2-DM and to induce higher levels of pigmentation. Both 5-NBene-2,2-DM and 2,3-cs/ex-PinD induce synthesis of nitric oxide (NO) in S91 cells, and the melanogenic activity of both compounds is reduced by inhibitors of the NO/cyclic guanosine monophosphate (cGMP)/protein kinase(PK) G signaling pathway, but not by inhibitors of the PKC or PKA pathways. Thus, these bicyclic monoterpene diols appear to induce melanogenesis by the same pathway in S91 cells as that shown previously for ultraviolet radiation in melanocytes (Romero-Graillet et al. (1996) J. Biol. Chem., 271:28052-28056). These compounds also induce NO synthesis, neurite outgrowth, and tyrosine hydroxylase activity in PC12 pheochromocytoma cells. Neurite outgrowth in PC12 cells is blocked by the guanylate cyclase inhibitor, LY83583 (6-anilino-2,8-quinolinequinone), indicating that, similar to S91 cells, the induction of morphological differentiation of PC12 cells by bicyclic monoterpene diols is regulated by a cGMP-dependent pathway.

  19. Clinical value of {sup 18}F-fluorodihydroxyphenylalanine positron emission tomography/computed tomography ({sup 18}F-DOPA PET/CT) for detecting pheochromocytoma

    Energy Technology Data Exchange (ETDEWEB)

    Luster, Markus; Zeich, Katrin; Glatting, Gerhard; Buck, Andreas K.; Solbach, Christoph; Reske, Sven N. [University of Ulm, Department of Nuclear Medicine, Ulm (Germany); Karges, Wolfram [RWTH Aachen, Division of Endocrinology and Diabetes, Aachen (Germany); Pauls, Sandra [University of Ulm, Department of Radiology, Ulm (Germany); Verburg, Frederik A. [University of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); Dralle, Henning [University Halle-Wittenberg, Department of General, Visceral and Vascular Surgery, Halle (Germany); Neumaier, Bernd [University of Ulm, Department of Nuclear Medicine, Ulm (Germany); Max-Planck-Institut fuer Neurologische Forschung, Section for Radiochemistry, Cologne (Germany); Mottaghy, Felix M. [University of Ulm, Department of Nuclear Medicine, Ulm (Germany); RWTH Aachen, Department of Nuclear Medicine, Aachen (Germany)

    2010-03-15

    In detecting pheochromocytoma (PHEO), positron emission tomography (PET) with the radiolabelled amine precursor {sup 18}F-fluorodihydroxyphenylalanine ({sup 18}F-DOPA) offers excellent specificity, while computed tomography (CT) provides high sensitivity and ability to localize lesions; therefore, the combination of these modalities could be advantageous in this setting. The aim of this study was to investigate whether combined {sup 18}F-DOPA PET/CT more accurately detects and localizes PHEO lesions than does each modality alone. {sup 18}F-DOPA PET, CT and {sup 18}F-DOPA PET/CT images of 25 consecutive patients undergoing diagnostic scanning of suspected sporadic or multiple endocrine neoplasia type 2 syndrome-associated PHEO were reviewed retrospectively in randomized sequence. Two blinded observers scored the images regarding the likelihood of PHEO being present and localizable. Results were correlated with subsequent clinical history and, when available, histology. Of the 19 lesions detected by all three modalities, PET identified each as positive for PHEO, but was unable to definitively localize 15 of 19 (79%). CT could definitively localize all 19 lesions, but could not definitively diagnose or exclude PHEO in 18 of 19 (95%) lesions. Furthermore, CT falsely identified as negative for PHEO one lesion which was judged to be positive for this tumor by both PET and PET/CT. Only in PET/CT scans were all 19 lesions accurately characterized and localized. On a per-patient basis, the sensitivity of {sup 18}F-DOPA PET/CT for PHEO was 100% and the specificity 88%, with a 100% positive predictive value and an 88% negative predictive value. {sup 18}F-DOPA PET/CT more accurately diagnoses and localizes adrenal and extra-adrenal masses suspicious for PHEO than do {sup 18}F-DOPA PET or CT alone. (orig.)

  20. Clinical value of 18F-fluorodihydroxyphenylalanine positron emission tomography/computed tomography (18F-DOPA PET/CT) for detecting pheochromocytoma

    International Nuclear Information System (INIS)

    Luster, Markus; Zeich, Katrin; Glatting, Gerhard; Buck, Andreas K.; Solbach, Christoph; Reske, Sven N.; Karges, Wolfram; Pauls, Sandra; Verburg, Frederik A.; Dralle, Henning; Neumaier, Bernd; Mottaghy, Felix M.

    2010-01-01

    In detecting pheochromocytoma (PHEO), positron emission tomography (PET) with the radiolabelled amine precursor 18 F-fluorodihydroxyphenylalanine ( 18 F-DOPA) offers excellent specificity, while computed tomography (CT) provides high sensitivity and ability to localize lesions; therefore, the combination of these modalities could be advantageous in this setting. The aim of this study was to investigate whether combined 18 F-DOPA PET/CT more accurately detects and localizes PHEO lesions than does each modality alone. 18 F-DOPA PET, CT and 18 F-DOPA PET/CT images of 25 consecutive patients undergoing diagnostic scanning of suspected sporadic or multiple endocrine neoplasia type 2 syndrome-associated PHEO were reviewed retrospectively in randomized sequence. Two blinded observers scored the images regarding the likelihood of PHEO being present and localizable. Results were correlated with subsequent clinical history and, when available, histology. Of the 19 lesions detected by all three modalities, PET identified each as positive for PHEO, but was unable to definitively localize 15 of 19 (79%). CT could definitively localize all 19 lesions, but could not definitively diagnose or exclude PHEO in 18 of 19 (95%) lesions. Furthermore, CT falsely identified as negative for PHEO one lesion which was judged to be positive for this tumor by both PET and PET/CT. Only in PET/CT scans were all 19 lesions accurately characterized and localized. On a per-patient basis, the sensitivity of 18 F-DOPA PET/CT for PHEO was 100% and the specificity 88%, with a 100% positive predictive value and an 88% negative predictive value. 18 F-DOPA PET/CT more accurately diagnoses and localizes adrenal and extra-adrenal masses suspicious for PHEO than do 18 F-DOPA PET or CT alone. (orig.)

  1. Plasma methoxytyramine: a novel biomarker of metastatic pheochromocytoma and paraganglioma in relation to established risk factors of tumour size, location and SDHB mutation status.

    Science.gov (United States)

    Eisenhofer, Graeme; Lenders, Jacques W M; Siegert, Gabriele; Bornstein, Stefan R; Friberg, Peter; Milosevic, Dragana; Mannelli, Massimo; Linehan, W Marston; Adams, Karen; Timmers, Henri J; Pacak, Karel

    2012-07-01

    There are currently no reliable biomarkers for malignant pheochromocytomas and paragangliomas (PPGLs). This study examined whether measurements of catecholamines and their metabolites might offer utility for this purpose. Subjects included 365 patients with PPGLs, including 105 with metastases, and a reference population of 846 without the tumour. Eighteen catecholamine-related analytes were examined in relation to tumour location, size and mutations of succinate dehydrogenase subunit B (SDHB). Receiver-operating characteristic curves indicated that plasma methoxytyramine, the O-methylated metabolite of dopamine, provided the most accurate biomarker for discriminating patients with and without metastases. Plasma methoxytyramine was 4.7-fold higher in patients with than without metastases, a difference independent of tumour burden and the associated 1.6- to 1.8-fold higher concentrations of norepinephrine and normetanephrine. Increased plasma methoxytyramine was associated with SDHB mutations and extra-adrenal disease, but was also present in patients with metastases without SDHB mutations or those with metastases secondary to adrenal tumours. High risk of malignancy associated with SDHB mutations reflected large size and extra-adrenal locations of tumours, both independent predictors of metastatic disease. A plasma methoxytyramine above 0.2nmol/L or a tumour diameter above 5cm indicated increased likelihood of metastatic spread, particularly when associated with an extra-adrenal location. Plasma methoxytyramine is a novel biomarker for metastatic PPGLs that together with SDHB mutation status, tumour size and location provide useful information to assess the likelihood of malignancy and manage affected patients. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. Plasma methoxytyramine: A novel biomarker of metastatic pheochromocytoma and paraganglioma in relation to established risk factors of tumor size, location and SDHB mutation status

    Science.gov (United States)

    Eisenhofer, Graeme; Lenders, Jacques W.M.; Siegert, Gabriele; Bornstein, Stefan R.; Friberg, Peter; Milosevic, Dragana; Mannelli, Massimo; Linehan, W. Marston; Adams, Karen; Timmers, Henri J.; Pacak, Karel

    2012-01-01

    Summary Background There are currently no reliable biomarkers for malignant pheochromocytomas and paragangliomas (PPGLs). This study examined whether measurements of catecholamines and their metabolites might offer utility for this purpose. Methods Subjects included 365 patients with PPGLs, including 105 with metastases, and a reference population of 846 without the tumor. Eighteen catecholamine-related analytes were examined in relation to tumor location, size and mutations of succinate dehydrogenase subunit B (SDHB). Results Receiver-operating characteristic curves indicated that plasma methoxytyramine, the O-methylated metabolite of dopamine, provided the most accurate biomarker for discriminating patients with and without metastases. Plasma methoxytyramine was 4.7-fold higher in patients with than without metastases, a difference independent of tumor burden and the associated 1.6- to 1.8-fold higher concentrations of norepinephrine and normetanephrine. Increased plasma methoxytyramine was associated with SDHB mutations and extra-adrenal disease, but was also present in patients without SDHB mutations and metastases or those with metastases secondary to adrenal tumors. High risk of malignancy associated with SDHB mutations reflected large size and extra-adrenal locations of tumors, both independent predictors of metastatic disease. A plasma methoxytyramine above 0.2 nmol/L or a tumor diameter above 5 cm indicated increased likelihood of metastatic spread, particularly when associated with an extra-adrenal location. Interpretation Plasma methoxytyramine is a novel biomarker for metastatic PPGLs that together with SDHB mutation status, tumor size and location provide useful information to assess the likelihood of malignancy and manage affected patients. PMID:22036874

  3. {sup 18}F-fluorodihydroxyphenylalanine PET/CT in pheochromocytoma and paraganglioma: relation to genotype and amino acid transport system L

    Energy Technology Data Exchange (ETDEWEB)

    Feral, Chloe C.; Tissot, Floriane S.; Tosello, Lionel [INSERM U1081, Institute for Research on Cancer and Aging of Nice (IRCAN), Nice (France); Fakhry, Nicolas [Aix-Marseille University, Department of Otorhinolaryngology-Head and Neck Surgery, Conception Hospital, Marseille (France); Sebag, Frederic [Aix-Marseille University, Department of Endocrine Surgery, Conception Hospital, Marseille (France); Pacak, Karel [Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD (United States); Taieb, David [Aix-Marseille University, Department of Nuclear Medicine, La Timone University Hospital, CERIMED, Marseille (France)

    2017-05-15

    F-FDOPA is a highly sensitive and specific radiopharmaceutical for pheochromocytoma and paraganglioma (PPGL) imaging. However, {sup 18}F-FDOPA might be falsely negative in these tumors, especially those related to mutations in succinate dehydrogenase genes (SDHx). The aim of the present study was to evaluate the relationship between expression of L-DOPA transporters and {sup 18}F-FDOPA PET imaging results in PPGL. From 2007 to 2015, 175 patients with non-metastatic PPGL were evaluated by {sup 18}F-FDOPA PET/CT for initial diagnosis/staging and follow-up. {sup 18}F-FDOPA PET/CT was considered as falsely negative for at least one lesion in 10/126 (8%) patients (two sporadic, six SDHD, two SDHB PPGLs). The mRNA and protein expression levels of CD98hc and LATs were evaluated in samples with different genetic backgrounds and imaging phenotypes. The qRT-PCR and immunohistochemical analyses were performed in 14 and 16 tumor samples, respectively. The SDHx mutated samples exhibited a significant decrease in mRNA expression of LAT3 when compared to sporadic PPGLs (P = 0.042). There was also a statistical trend toward decreased CD98hc (P = 0.147) and LAT4 (P = 0.012) levels in SDHx vs sporadic PPGLs. No difference was observed for LAT1/LAT2 mRNA levels. LAT1 protein was expressed in 15 out of 16 (93.75%) SDHx tumors, regardless of the {sup 18}F-FDOPA positivity. LAT1 and CD98hc were co-expressed in 6/8 {sup 18}F-FDOPA-negative PPGLs. In contrast, in one case with absence of LAT1/CD98hc, {sup 18}F-FDOPA uptake was positive and attributed to LAT4 expression. We conclude that down-regulation of LAT1/CD98hc cannot explain the imaging phenotype of SDHx-related PPGLs. A reduced activity of LAT1 remains the primary hypothesis possibly due to a modification of intracellular amino acid content which may reduce {sup 18}F-FDOPA uptake. (orig.)

  4. PET/CT comparing 68Ga-DOTATATE and other radiopharmaceuticals and in comparison with CT/MRI for the localization of sporadic metastatic pheochromocytoma and paraganglioma

    International Nuclear Information System (INIS)

    Janssen, Ingo; Chen, Clara C.; Millo, Corina M.; Herscovitch, Peter; Ling, Alexander; Taieb, David; Lin, Frank I.; Adams, Karen T.; Wolf, Katherine I.; Pacak, Karel; Fojo, Antonio T.; Buchmann, Inga; Kebebew, Electron

    2016-01-01

    Pheochromocytomas/paragangliomas (PPGLs) and their metastases are tumors that predominantly express somatostatin receptor 2 (SSR2). 68 Ga-DOTA(0)-Tyr(3)-octreotate ( 68 Ga-DOTATATE) is a PET radiopharmaceutical with both high and selective affinity for SSRs. The purpose of this study was to evaluate the utility of 68 Ga-DOTATATE in comparison with other specific and nonspecific radiopharmaceuticals recommended in the current guidelines for the localization of metastatic sporadic PPGL by PET/CT. This prospective study included 22 patients (15 men, 7 women; aged 50.0 ± 13.9 years) with confirmed metastatic PPGL, a negative family history for PPGL, and negative genetic testing, who underwent 68 Ga-DOTATATE, 18 F-fluoro-2-deoxy-D-glucose ( 18 F-FDG) PET/CT, and CT/MRI. Only 12 patients underwent an additional 18 F-fluorodihydroxyphenylalanine ( 18 F-FDOPA) PET/CT scan and only 11 patients underwent an additional 18 F-fluorodopamine ( 18 F-FDA) PET/CT scan. The rates of detection of metastatic lesions were compared among all the imaging studies. A composite of all functional and anatomical imaging studies served as the imaging comparator. 68 Ga-DOTATATE PET/CT showed a lesion-based detection rate of 97.6 % (95 % confidence interval, CI, 95.8 - 98.7 %). 18 F-FDG PET/CT, 18 F-FDOPA PET/CT, 18 F-FDA PET/CT, and CT/MRI showed detection rates of 49.2 % (CI 44.5 - 53.6 %; p < 0.01), 74.8 % (CI 69.0 - 79.9 %; p < 0.01), 77.7 % (CI 71.5 - 82.8 %; p < 0.01), and 81.6 % (CI 77.8 - 84.8 %; p < 0.01), respectively. The results of this study demonstrate the superiority of 68 Ga-DOTATATE PET/CT in the localization of sporadic metastatic PPGLs compared to all other functional and anatomical imaging modalities, and suggest modification of future guidelines towards this new imaging modality. (orig.)

  5. Chronic ingestion of 2-deoxy-D-glucose induces cardiac vacuolization and increases mortality in rats

    International Nuclear Information System (INIS)

    Minor, Robin K.; Smith, Daniel L.; Sossong, Alex M.; Kaushik, Susmita; Poosala, Suresh; Spangler, Edward L.; Roth, George S.; Lane, Mark; Allison, David B.; Cabo, Rafael de; Ingram, Donald K.; Mattison, Julie A.

    2010-01-01

    Calorie restriction (CR), the purposeful reduction of energy intake with maintenance of adequate micronutrient intake, is well known to extend the lifespan of laboratory animals. Compounds like 2-deoxy-D-glucose (2DG) that can recapitulate the metabolic effects of CR are of great interest for their potential to extend lifespan. 2DG treatment has been shown to have potential therapeutic benefits for treating cancer and seizures. 2DG has also recapitulated some hallmarks of the CR phenotype including reduced body temperature and circulating insulin in short-term rodent trials, but one chronic feeding study in rats found toxic effects. The present studies were performed to further explore the long-term effects of 2DG in vivo. First we demonstrate that 2DG increases mortality of male Fischer-344 rats. Increased incidence of pheochromocytoma in the adrenal medulla was also noted in the 2DG treated rats. We reconfirm the cardiotoxicity of 2DG in a 6-week follow-up study evaluating male Brown Norway rats and a natural form of 2DG in addition to again examining effects in Fischer-344 rats and the original synthetic 2DG. High levels of both 2DG sources reduced weight gain secondary to reduced food intake in both strains. Histopathological analysis of the hearts revealed increasing vacuolarization of cardiac myocytes with dose, and tissue staining revealed the vacuoles were free of both glycogen and lipid. We did, however, observe higher expression of both cathepsin D and LC3 in the hearts of 2DG-treated rats which indicates an increase in autophagic flux. Although a remarkable CR-like phenotype can be reproduced with 2DG treatment, the ultimate toxicity of 2DG seriously challenges 2DG as a potential CR mimetic in mammals and also raises concerns about other therapeutic applications of the compound.

  6. treated rats

    African Journals Online (AJOL)

    aghomotsegin

    2014-01-08

    Jan 8, 2014 ... nucleus, bizarre segmentation; (I) shows hypersegmentation, bizarre segmentation of neutrophils in the shape of ring nucleus with polychromatophilic RBCs. 1998; Muller and Tobin, 1980). The current study shows that rats administered C. edulis hydro-ethanol extract, orally for 28 days, developed anemia, ...

  7. Metastatic adrenal pheochromocytoma to the thoracic spine Feocromocitoma adrenal metastásico para la columna torácica Feocromocitoma adrenal metastático para a coluna torácica

    Directory of Open Access Journals (Sweden)

    Michael T. Scalfani

    2010-09-01

    Full Text Available To report on a case of pheochromocytoma metastases to the spine occurring more than 20 years after initial diagnosis. A 34-year-old female with a history of metastatic pheochromocytoma diagnosed at age 12 presented with weakness, heart palpitations, and circumferential back pain of five months duration. The patient had undergone multiple laparatomies for abdominal and hepatic metastases. Work-up revealed a destructive lesion at T9. After two weeks of preoperative phenoxybenzamine to control her hypertension, she underwent decompression, posterior fixation and fusion. Surgical intervention was followed by radiation therapy, zoledronic acid, and only one cycle of chemotherapy due to intolerance of side effects. The patient survived 25 years after original diagnosis, which far exceeds the average survival of less than 15 years. The patient died 26 months postoperatively due to progression of disease. Pheochromocytoma with spine metastases occurring more than 20 years after diagnosis is very uncommon, and should be considered in the differential diagnosis of a patient with a history of pheochromocytoma.Relato de un caso de feocromocitoma adrenal con metástasis para la columna que ocurrió con más de 20 años de diagnóstico inicial. Mujer de 34 años con historia de feocromocitoma metastásico diagnosticado en la edad de 12 años, con presencia de debilidad, palpitaciones del corazón y dolor en la espalda circunferencial, con evolución de cinco meses. A la paciente se le había realizado diversas laparotomías por causa de metástasis abdominales y hepáticas. Durante la inspección, se mostró una lesión destructiva en T9. Después de dos semanas de fenoxibenzamina preoperatoria para controlar la hipertensión, se sometió a descompresión, fijación y posterior fusión. La intervención quirúrgica fue seguida por radioterapia, ácido zoledrónico, y sólo un ciclo de quimioterapia, debido a la intolerancia y a los efectos colaterales

  8. Exenatide Facilitates Recovery from Oxaliplatin-Induced Peripheral Neuropathy in Rats.

    Directory of Open Access Journals (Sweden)

    Shunsuke Fujita

    Full Text Available Oxaliplatin has widely been used as a key drug in the treatment of colorectal cancer; however, it causes peripheral neuropathy. Exenatide, a glucagon-like peptide-1 (GLP-1 agonist, is an incretin mimetic secreted from ileal L cells, which is clinically used to treat type 2 diabetes mellitus. GLP-1 receptor agonists have been reported to exhibit neuroprotective effects on the central and peripheral nervous systems. In this study, we investigated the effects of exenatide on oxaliplatin-induced neuropathy in rats and cultured cells.Oxaliplatin (4 mg/kg was administered intravenously twice per week for 4 weeks, and mechanical allodynia was evaluated using the von Frey test in rats. Axonal degeneration was assessed by toluidine blue staining of sciatic nerves.Repeated administration of oxaliplatin caused mechanical allodynia from day 14 to 49. Although the co-administration of extended-release exenatide (100 μg/kg could not inhibit the incidence of oxaliplatin-induced mechanical allodynia, it facilitated recovery from the oxaliplatin-induced neuropathy with reparation of axonal degeneration. Inhibition of neurite outgrowth was evaluated in cultured pheochromocytoma 12 (PC12 cells. Exenatide inhibited oxaliplatin-induced neurite degeneration, but did not affect oxaliplatin-induced cell injury in cultured PC12 cells. Additionally, extended-release exenatide had no effect on the anti-tumor activity of oxaliplatin in cultured murine colon adenocarcinoma 26 (C-26 cells or C-26 cell-implanted mice.These results suggest that exenatide may be useful for treating peripheral neuropathy induced by oxaliplatin in colorectal cancer patients with type 2 diabetes.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Rat Genome Database (RGD)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Rat Genome Database (RGD) is a collaborative effort between leading research institutions involved in rat genetic and genomic research to collect, consolidate,...

  11. Prospective comparison of {sup 68}Ga-DOTATATE and {sup 18}F-FDOPA PET/CT in patients with various pheochromocytomas and paragangliomas with emphasis on sporadic cases

    Energy Technology Data Exchange (ETDEWEB)

    Archier, Aurelien; Taieb, David [Aix-Marseille University, Department of Nuclear Medicine, La Timone and North University Hospital, Marseille (France); Aix-Marseille University, European Center for Research in Medical Imaging, Marseille (France); Inserm UMR1068 Marseille Cancerology Research Center, Institut Paoli-Calmettes, Marseille (France); Varoquaux, Arthur; Beschmout, Eva [Aix-Marseille University, Department of Medical Imaging, Conception Hospital, Marseille (France); Garrigue, Philippe; Guillet, Benjamin [Aix-Marseille University, Department of Nuclear Medicine, La Timone and North University Hospital, Marseille (France); Aix-Marseille University, Department of Radiopharmacy, La Timone and North University Hospital, Marseille (France); Montava, Marion; Fakhry, Nicolas [Aix-Marseille University, Department of Otorhinolaryngology-Head and Neck Surgery, Conception Hospital, Marseille (France); Guerin, Carole; Sebag, Frederic [Aix-Marseille University, Department of Endocrine Surgery, Conception Hospital, Marseille (France); Gabriel, Sophie [Aix-Marseille University, Department of Nuclear Medicine, La Timone and North University Hospital, Marseille (France); Aix-Marseille University, European Center for Research in Medical Imaging, Marseille (France); Morange, Isabelle; Castinetti, Frederic [Aix-Marseille University, Department of Endocrinology, Conception Hospital, Marseille (France); Barlier, Anne [Aix-Marseille, University, Laboratory of Biochemistry and Molecular Biology, Conception Hospital, Marseille (France); Loundou, Anderson [Aix-Marseille University, Department of Public Health, Marseille (France); Pacak, Karel [National Institutes of Health, Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Bethesda, MD (United States)

    2016-07-15

    Pheochromocytomas/paragangliomas (PHEOs/PGLs) overexpress somatostatin receptors and recent studies have already shown excellent results in the localization of these tumors using {sup 68}Ga-labeled somatostatin analogs ({sup 68}Ga-DOTA-SSA), especially in patients with germline succinate dehydrogenase subunit B gene (SDHB) mutations and head and neck PGLs (HNPGLs). The value of {sup 68}Ga-DOTA-SSA has to be established in sporadic cases, including PHEOs. Thus, the aim of this study was to compare {sup 68}Ga-DOTATATE PET/CT, {sup 18}F-FDOPA PET/CT, and conventional imaging in patients with various PHEOs/PGLs with a special emphasis on sporadic cases, including those located in the adrenal gland. {sup 68}Ga-DOTATATE, {sup 18}F-FDOPA PET/CT, and conventional imaging (contrast-enhanced CT and MRI with MR angiography sequences) were prospectively performed in 30 patients (8 with SDHD mutations, 1 with a MAX mutation and 21 sporadic cases) with PHEO/PGL at initial diagnosis or relapse. The patient-based sensitivities were 93 % (28/30), 97 % (29/30), and 93 % (28/30) for {sup 68}Ga-DOTATATE PET/CT, {sup 18}F-FDOPA PET/CT, and conventional imaging, respectively. The lesion-based sensitivities were 93 % (43/46), 89 % (41/46), and 76 % (35/46) for {sup 68}Ga-DOTATATE PET/CT, {sup 18}F-FDOPA PET/CT, and conventional imaging respectively (p = 0.042). {sup 68}Ga-DOTATATE PET/CT detected a higher number of HNPGLs (30/30) than {sup 18}F-FDOPA PET/CT (26/30; p = 0.112) and conventional imaging (24/30; p = 0.024). {sup 68}Ga-DOTATATE PET/CT missed two PHEOs of a few millimeters in size and a large recurrent PHEO. One lesion was considered false-positive on {sup 68}Ga-DOTATATE PET/CT and corresponded to a typical focal lesion of fibrous dysplasia on MRI. Among the 11 lesions missed by conventional imaging, 7 were detected by conventional imaging with knowledge of the PET results (4 HNPGLs, 2 LNs, and 1 recurrent PHEO). {sup 68}Ga-DOTATATE PET/CT is the most sensitive tool in the

  12. SWEEP Project RAT

    DEFF Research Database (Denmark)

    Ibsen, Lars Bo; Madsen, Søren; Petersen, L. B.

    This report presents the results from the design analyses made for the clustered suction caisson used as foundation for a Riser Access Tower (RAT). The RAT is intended built next to the K15-FA-1 Platform in the Dutch Sector of the North Sea.......This report presents the results from the design analyses made for the clustered suction caisson used as foundation for a Riser Access Tower (RAT). The RAT is intended built next to the K15-FA-1 Platform in the Dutch Sector of the North Sea....

  13. Molecular Pathogenesis of Pheochromocytomas and Paragangliomash

    NARCIS (Netherlands)

    H. Dannenberg (Hilde)

    2005-01-01

    textabstractGeneral aspectsParaganglia are small neuroendocrine organs, that usually manifest as anatomically discrete bodies, the parenchymal cells of which are neural crest-derived, and produce catecholamines and various peptides. One group of paraganglia is aligned to the sympathoadrenal and

  14. What Are Common Symptoms of Pheochromocytoma?

    Science.gov (United States)

    ... Español NICHD Theme Browse AZTopics Browse A-Z Adrenal Gland Disorders Autism Spectrum Disorder (ASD) Down Syndrome Endometriosis Learning ... Funding Opportunities & Notices Health A to Z List Adrenal Gland Disorders About NICHD Research Information Find a Study More ...

  15. How Do Health Care Providers Diagnose Pheochromocytoma?

    Science.gov (United States)

    ... Español NICHD Theme Browse AZTopics Browse A-Z Adrenal Gland Disorders Autism Spectrum Disorder (ASD) Down Syndrome Endometriosis Learning ... Funding Opportunities & Notices Health A to Z List Adrenal Gland Disorders About NICHD Research Information Find a Study More ...

  16. Genetics Home Reference: hereditary paraganglioma-pheochromocytoma

    Science.gov (United States)

    ... 295(6):628. Citation on PubMed Selak MA, Armour SM, MacKenzie ED, Boulahbel H, Watson DG, Mansfield ... qualified healthcare professional . About Selection Criteria for Links Data Files & API Site Map Subscribe Customer Support USA. ...

  17. Rat Bite Fever

    Science.gov (United States)

    ... Español Text Size Email Print Share Rat Bite Fever Page Content Article Body Rat-bite fever is a disease that occurs in humans who ... ingestion of contaminated food or milk products (Haverhill fever). Most cases in the United States are caused ...

  18. Colon of the rat

    International Nuclear Information System (INIS)

    Lindstroem, C.G.; Rosengren, J.-E.; Fork, F.-T.

    1979-01-01

    The anatomy and radiologic appearance of the colon in rats are described on the basis of 300 animals treated with carcinogenic agents and 40 normal rats. The macroscopic and microscopic appearance of the mucosa varies in the different parts of the colon. Lymphoid plaques are normal structures. The results justify a new anatomic nomenclature. (Auth.)

  19. Chronic toxic and carcinogenic effects of oral cadmium in the Noble (NBL/Cr) rat: induction of neoplastic and proliferative lesions of the adrenal, kidney, prostate, and testes.

    Science.gov (United States)

    Waalkes, M P; Anver, M R; Diwan, B A

    1999-10-29

    Based on the occurrence of pulmonary cancers in exposed populations, cadmium is classified as a human carcinogen. More controversial target sites for cadmium in humans include the prostate and kidney, where some studies have shown a link between cadmium and cancer. In Wistar rats cadmium induces tumors in the ventral prostate. The relevance of such lesions to humans is debated since the rat ventral lobe, unlike the dorsolateral lobe, has no embryological homolog in the human prostate. Cadmium has not been linked with renal tumors in rodents but is a potent nephrotoxin. In this work we studied the effects of oral cadmium in the Noble (NBL/Cr) rat with particular attention to proliferative lesions of the prostate and kidneys. Cadmium (as CdCl2) was given ad libitum throughout the study in the drinking water at doses of 0, 25, 50, 100, and 200 ppm Cd to groups (initial n = 30) of male rats, which were observed for up to 102 wk. At the lower doses of cadmium (cadmium exposure and most frequently showed three or more foci within each specimen. At higher doses, prostatic proliferative lesions declined to control levels. The loss of prostatic response at the higher doses was likely due to diminished testicular function secondary to cadmium treatment. This was reflected in lesions indicative of testicular hypofunction at the highest cadmium dose, namely, interstitial cell hyperplasia, and a strong correlation between cadmium dose and total proliferative lesions of the testes (hyperplasias and tumors combined). Renal tumors (mainly mesenchymal and pelvic transitional cell), although few in number, showed a positive correlation with cadmium dose, as did pelvic transitional epithelial hyperplasia. Renal lesions were not associated with any cadmium-induced changes in age-related chronic nephropathy. The incidence of pheochromocytomas of the adrenal was increased by cadmium but only at the 50 ppm dose. Inflammatory lesions of the liver and spleen were common at higher doses and

  20. In vitro effects of fetal rat cerebrospinal fluid on viability and neuronal differentiation of PC12 cells

    Directory of Open Access Journals (Sweden)

    Nabiuni Mohammad

    2012-06-01

    Full Text Available Abstract Background Fetal cerebrospinal fluid (CSF contains many neurotrophic and growth factors and has been shown to be capable of supporting viability, proliferation and differentiation of primary cortical progenitor cells. Rat pheochromocytoma PC12 cells have been widely used as an in vitro model of neuronal differentiation since they differentiate into sympathetic neuron-like cells in response to growth factors. This study aimed to establish whether PC12 cells were responsive to fetal CSF and therefore whether they might be used to investigate CSF physiology in a stable cell line lacking the time-specific response patterns of primary cells previously described. Methods In vitro assays of viability, proliferation and differentiation were carried out after incubation of PC12 cells in media with and without addition of fetal rat CSF. An MTT tetrazolium assay was used to assess cell viability and/or cell proliferation. Expression of neural differentiation markers (MAP-2 and β-III tubulin was determined by immunocytochemistry. Formation and growth of neurites was measured by image analysis. Results PC12 cells differentiate into neuronal cell types when exposed to bFGF. Viability and cell proliferation of PC12 cells cultured in CSF-supplemented medium from E18 rat fetuses were significantly elevated relative to the control group. Neuronal-like outgrowths from cells appeared following the application of bFGF or CSF from E17 and E19 fetuses but not E18 or E20 CSF. Beta-III tubulin was expressed in PC12 cells cultured in any media except that supplemented with E18 CSF. MAP-2 expression was found in control cultures and in those with E17 and E19 CSF. MAP2 was located in neurites except in E17 CSF when the whole cell was positive. Conclusions Fetal rat CSF supports viability and stimulates proliferation and neurogenic differentiation of PC12 cells in an age-dependent way, suggesting that CSF composition changes with age. This feature may be important

  1. Longtransplantatie bij de rat

    NARCIS (Netherlands)

    Marck, Klaas Willem

    1983-01-01

    Op grond van de resultaten van het hierboven beschreven onderzoek en de eraan gewijde beschouwingen zijn de volgende conclasies getrokken: 1. Orthotope linkszijdige longtransplantatie bij de rat is operatietechnisch mogelijk. 2. Longpercusiescintigrafie met radioactief ,,gelabelde" microbolletjes is

  2. Rat-bite fever

    Science.gov (United States)

    Streptobacillary fever; Streptobacillosis; Haverhill fever; Epidemic arthritic erythema; Spirillary fever; Sodoku ... Rat-bite fever can be caused by either of 2 different bacteria, Streptobacillus moniliformis or Spirillum minus. Both of these are ...

  3. Crise de feocromocitoma simulando um infarto agudo do miocárdio em paciente com artérias coronárias normais Pheochromocytoma-induced segmental myocardial dysfunction mimicking an acute myocardial infarction in a patient with normal coronary arteries

    Directory of Open Access Journals (Sweden)

    Eduardo S. Darzé

    2004-02-01

    Full Text Available Relatamos o caso de um paciente com alterações eletrocardiográficas e disfunção miocárdica segmentar induzidas por feocromocitoma, simulando infarto agudo do miocárdio. A angiografia coronariana foi normal e houve normalização completa do eletrocardiograma e ecocardiograma, após terapia com um bloqueador alfa-adrenérgico e ressecção do tumor. Espasmo coronariano foi o provável mecanismo envolvido na produção dessas alterações, ilustrando a importância de manter um alto grau de suspeição clínica em pacientes com evento miocárdico inesperado em meio a uma crise hipertensiva.We report a case of pheochromocytoma-induced segmental myocardial dysfunction and electrocardiographic abnormalities mimicking an acute anterior myocardial infarction, probably due to coronary spasm. Coronary angiography showed normal coronaries, and the electrocardiographic and echocardiographic changes resolved completely after therapy with an alpha-adrenergic blocker and tumor removal. Our case illustrates the importance of maintaining a high index of suspicion in patients presenting with an unexpected myocardial event and a hypertensive crisis.

  4. The academic rat race

    DEFF Research Database (Denmark)

    Landes, Xavier; Andersen, Martin Marchman; Nielsen, Morten Ebbe Juul

    2012-01-01

    : an increased pressure to produce articles (in peer-reviewed journals) has created an unbalanced emphasis on the research criterion at the expense of the latter two. More fatally, this pressure has turned academia into a rat race, leading to a deep change in the fundamental structure of academic behaviour...

  5. in albino rats

    African Journals Online (AJOL)

    hope&shola

    2010-09-23

    Sep 23, 2010 ... cell carcinoma (02) and malignant fibrous histiocytoma. (02) (Figures 1 and 2). Most of the rats had chronic inflammation and precancerous changes in early weeks. Figure 3. Photomicrograph showing normal epidermal and dermal layers (H & E X 100). Hair loss was observed on specific areas on the third.

  6. CAMALDULENSIS IN RATS

    African Journals Online (AJOL)

    DR. AMIN

    ABSTRACT. Sub – acute toxicity study of the aqueous leaf extract of Eucalyptus camaldulensis was carried out on albino rats. Doses of 250mg, 500mg, 750mg and 1000mg per kilogram body weight of the extract were administered orally for 21 days. The activities of Alanine Aminotransferase (ALT),. Aspartate ...

  7. Attachment behavior in rats

    NARCIS (Netherlands)

    Sigling, H.O.

    2009-01-01

    This thesis describes studies into the rat as an animal model for attachment, along the lines of Bowlby's attachment theory. First, the relation between attachment and human psychopathology is reviewed. The conclusion is that psychopathology is more frequent in insecure attached persons and that

  8. Rat bite fever.

    NARCIS (Netherlands)

    Gaastra, W.; Boot, R.G.A.; Ho, H.; Lipman, L.J.A.

    2009-01-01

    Rat bite fever (RBF) is a bacterial zoonosis for which two causal bacterial species have been identified: Streptobacillis moniliformis and Spirillum minus. Haverhill fever (HF) is a form of S. moniliformis infection believed to develop after ingestion of contaminated food or water. Here the

  9. Tubuloglomerular feedback in Dahl rats

    DEFF Research Database (Denmark)

    Karlsen, F M; Leyssac, P P; Holstein-Rathlou, N H

    1998-01-01

    We have previously demonstrated a loss of autoregulation in Dahl salt-sensitive (Dahl-S) rats rendered hypertensive on a high-salt diet. To determine whether this was due to a decreased activity of either the myogenic or the tubuloglomerular feedback (TGF) response, we tested the TGF response...... in both Dahl-S and salt-resistant Dahl rats on high- and low-salt diets. TGF was investigated in the closed-loop mode with a videometric technique, in which the response in late proximal flow rate to perturbations in Henle flow rate was measured. All Dahl rats showed a similar compensatory response...... to perturbations around the natural operating point, with a TGF response that was more efficient than in normotensive Sprague-Dawley rats. No evidence of decreased TGF responsiveness in hypertensive Dahl-S rats was found. The results suggest that the loss of autoregulation in hypertensive Dahl-S rats is due...

  10. Rat Genome and Model Resources.

    Science.gov (United States)

    Shimoyama, Mary; Smith, Jennifer R; Bryda, Elizabeth; Kuramoto, Takashi; Saba, Laura; Dwinell, Melinda

    2017-07-01

    Rats remain a major model for studying disease mechanisms and discovery, validation, and testing of new compounds to improve human health. The rat's value continues to grow as indicated by the more than 1.4 million publications (second to human) at PubMed documenting important discoveries using this model. Advanced sequencing technologies, genome modification techniques, and the development of embryonic stem cell protocols ensure the rat remains an important mammalian model for disease studies. The 2004 release of the reference genome has been followed by the production of complete genomes for more than two dozen individual strains utilizing NextGen sequencing technologies; their analyses have identified over 80 million variants. This explosion in genomic data has been accompanied by the ability to selectively edit the rat genome, leading to hundreds of new strains through multiple technologies. A number of resources have been developed to provide investigators with access to precision rat models, comprehensive datasets, and sophisticated software tools necessary for their research. Those profiled here include the Rat Genome Database, PhenoGen, Gene Editing Rat Resource Center, Rat Resource and Research Center, and the National BioResource Project for the Rat in Japan. © The Author 2017. Published by Oxford University Press.

  11. Laughing rats are optimistic.

    Directory of Open Access Journals (Sweden)

    Rafal Rygula

    Full Text Available Emotions can bias human decisions- for example depressed or anxious people tend to make pessimistic judgements while those in positive affective states are often more optimistic. Several studies have reported that affect contingent judgement biases can also be produced in animals. The animals, however, cannot self-report; therefore, the valence of their emotions, to date, could only be assumed. Here we present the results of an experiment where the affect-contingent judgement bias has been produced by objectively measured positive emotions. We trained rats in operant Skinner boxes to press one lever in response to one tone to receive a food reward and to press another lever in response to a different tone to avoid punishment by electric foot shock. After attaining a stable level of discrimination performance, the animals were subjected to either handling or playful, experimenter-administered manual stimulation - tickling. This procedure has been confirmed to induce a positive affective state in rats, and the 50-kHz ultrasonic vocalisations (rat laughter emitted by animals in response to tickling have been postulated to index positive emotions akin to human joy. During the tickling and handling sessions, the numbers of emitted high-frequency 50-kHz calls were scored. Immediately after tickling or handling, the animals were tested for their responses to a tone of intermediate frequency, and the pattern of their responses to this ambiguous cue was taken as an indicator of the animals' optimism. Our findings indicate that tickling induced positive emotions which are directly indexed in rats by laughter, can make animals more optimistic. We demonstrate for the first time a link between the directly measured positive affective state and decision making under uncertainty in an animal model. We also introduce innovative tandem-approach for studying emotional-cognitive interplay in animals, which may be of great value for understanding the emotional

  12. Do rats have orgasms?

    Directory of Open Access Journals (Sweden)

    James G. Pfaus

    2016-10-01

    Full Text Available Background: Although humans experience orgasms with a degree of statistical regularity, they remain among the most enigmatic of sexual responses; difficult to define and even more difficult to study empirically. The question of whether animals experience orgasms is hampered by similar lack of definition and the additional necessity of making inferences from behavioral responses. Method: Here we define three behavioral criteria, based on dimensions of the subjective experience of human orgasms described by Mah and Binik, to infer orgasm-like responses (OLRs in other species: 1 physiological criteria that include pelvic floor and anal muscle contractions that stimulate seminal emission and/or ejaculation in the male, or that stimulate uterine and cervical contractions in the female; 2 short-term behavioral changes that reflect immediate awareness of a pleasurable hedonic reward state during copulation; and 3 long-term behavioral changes that depend on the reward state induced by the OLR, including sexual satiety, the strengthening of patterns of sexual arousal and desire in subsequent copulations, and the generation of conditioned place and partner preferences for contextual and partner-related cues associated with the reward state. We then examine whether physiological and behavioral data from observations of male and female rats during copulation, and in sexually-conditioned place- and partner-preference paradigms, are consistent with these criteria. Results: Both male and female rats display behavioral patterns consistent with OLRs. Conclusions: The ability to infer OLRs in rats offers new possibilities to study the phenomenon in neurobiological and molecular detail, and to provide both comparative and translational perspectives that would be useful for both basic and clinical research.

  13. Serum testosterone concentration in chloroquinetreated rats: effects ...

    African Journals Online (AJOL)

    The effects of ascorbic acid (vitamin C) and alpha-tocopherol (vitamin E) were studied on serum testosterone concentration in chloroquine-treated rats. Thirty five (35) adult male rats weighing 160 - 200 g were divided into seven groups of five (5) rats each. Group I rats served as the control and received 2 ml/kg of normal ...

  14. Hexachlorophene retinopathy in rats.

    Science.gov (United States)

    Towfighi, J; Gonatas, N K; McCree, L

    1975-03-01

    The primary effect of hexachlorophene on rat retina is disruption of the disc membranes of photoreceptor outer segments and irreversible destruction of their cell bodies. The neurons of the ganglion cell layer of the retina also become affected, probably secondary to optic nerve lesions present in hexachlorophene intoxication. The early and probably reversible changes of the discs are vacuolation and vesiculotubular degeneration. Vacuolation in the discs results from separation of their inner aspects. This lesion is analogous to the separation of myelin lamellae at the intraperiod line, also produced by hexachlorophene.

  15. The academic rat race

    DEFF Research Database (Denmark)

    Landes, Xavier; Andersen, Martin Marchman; Nielsen, Morten Ebbe Juul

    2012-01-01

    : an increased pressure to produce articles (in peer-reviewed journals) has created an unbalanced emphasis on the research criterion at the expense of the latter two. More fatally, this pressure has turned academia into a rat race, leading to a deep change in the fundamental structure of academic behaviour......, and entailing a self-defeating and hence counter-productive pattern, where more publications is always better and where it becomes increasingly difficult for researchers to keep up with the new research in their field. The article identifies the pressure to publish as a problem of collective action. It ends up...

  16. The Rat Race

    CERN Multimedia

    Stephen Haywood

    Dear Muriel, Being an animal, you are probably more familiar with rats than most of us. Yet it seems to me that our Community (not just ATLAS) is stuck in a huge "rat race". I am somewhat mystified as to how we have got ourselves into this and I wonder whether you or your readers could explain this - I give my own observations below. In HEP and ATLAS specifically, we are all working long hours and we are all becoming exhausted. There are people at Point 1 who are working day and night, every day of the week; there are people writing software who send emails round the clock, including weekends. It is one thing to have bursts of activity which require us to put in some longer hours, but in ATLAS, the bursts last months or years. I have been on ATLAS 14 years and it has felt like one endless rush. Why do we do this? We are all highly motivated, we love our work and want to succeed individually and collectively. We are parts of various teams, and we do not want to let the side down. We worked hard at school an...

  17. Oxidative Stress in Aged Rats

    Directory of Open Access Journals (Sweden)

    Damisela Ramírez Ramírez

    2013-12-01

    Full Text Available Background: aging is one of the major problems that the world is facing today due to its impact on all areas of society. Objective: to determine the concentrations of advanced oxidation protein products and malondialdehyde as indicators of oxidative damage and to determine the antioxidant defense capacity of the enzymes superoxide dismutase, catalase and the reduced glutathione concentration in aged rats. Methods: a total of 20 male Wistar rats with a body weight of approximately 200 to 250 grams were selected to form two groups with 10 young adult rats and 10 old rats. 2 ml of blood was drawn from the paranasal sinus. The sample was collected in 5 ml vials and after being homogenized, it was sent to the Biomedical Research Center, where it was used to assess the following oxidative stress variables: degree of oxidative damage and antioxidant defense level. An analysis of variance was performed to study the behavior of the different groups. Differences were considered significant when P value was less than 0.05. Results: no significant changes were found in the concentrations of malondialdehyde and glutathione, as well as in the superoxide dismutase and catalase activity in aged rats compared to young. Concentration of advanced oxidation protein products increased significantly in aged rats. Conclusions: aged rats showed an increase in oxidative damage to proteins. Antioxidant defense capacity of the enzymes superoxide dismutase and catalase and reduced glutathione concentration showed no changes.

  18. Genetic Susceptibility Factors in Aggressive Breast Cancer in African-American Women and the Effects of Carcinogens and Modifiers.

    Science.gov (United States)

    1999-05-01

    site in rat pheochromocytoma (PC12) cells: Decreased affinity for (+)-benzomorphans and lower molecular weight suggest a different sigma receptor form...Hellewell, S.B., Bruce, A., Feinstein, G., Orringer, J., Williams, W., and Bowen, W.D. Rat liver and kidney contain high densities of sigma-1 and sigma-2...thyroid carcinoma (MTC) of the parafollicular C cells of thyroid, pheochromocytoma and hyperparathyroidism . MEN2B is similar to form 2A with the 64

  19. Rat traps: filling the toolbox for manipulating the rat genome

    NARCIS (Netherlands)

    van Boxtel, R.; Cuppen, E.

    2010-01-01

    The laboratory rat is rapidly gaining momentum as a mammalian genetic model organism. Although traditional forward genetic approaches are well established, recent technological developments have enabled efficient gene targeting and mutant generation. Here we outline the current status, possibilities

  20. Beta-endorphin in genetically hypoprolactinemic rat: IPL nude rat

    Energy Technology Data Exchange (ETDEWEB)

    Cohen, H.; Sabbagh, I.; Abou-Samra, A.B.; Bertrand, J.

    1986-01-20

    Beta-endorphin has been reported to regulate not only stress- and suckling-induced but also basal prolactin secretion. In the aim to better evaluate the endogenous beta-endorphin-prolactin interrelation, the authors measured beta-endorphin levels in a new rat strain, genetically hypoprolactinemic and characterized by a total lack of lactation: IPL nude rat. Beta-endorphin was measured using a specific anti-h-..beta.. endorphin in plasma and extracts of anterior and neurointermediate lobes of the pituitary, hypothalamus and brain. Pituitary extracts were also chromatographed on Sephadex G50 column. Results obtained showed that in IPL nude females on diestrus and males, the beta-endorphin contents of the neurointermediate lobe was significantly lower than in normal rats, while the values found in the other organs and plasma were similar. However, elution pattern of the anterior pituitary extracts from male rats showed greater immunoactivity eluting as I/sup 125/ h-beta-endorphin than in normal rat; this was not the case for the female rat. These results are consistent with a differential regulation of beta-endorphin levels of anterior and neurointermediate lobe by catecholamines. Moreover they suggest that PRL secretion was more related to neurointermediate beta-endorphin. 40 references, 2 figures, 4 tables.

  1. Intramitochondrial autonomy in rat tissues

    International Nuclear Information System (INIS)

    Subramanian, M.; Rajwade, M.S.; Satav, J.G.; Katyare, S.S.; Fatterpaker, P.; Sreenivasan, A.

    1974-01-01

    The biogenesis of mitochondria in rat liver and their protein turnover has been investigated using 1- 14 C leucine. The results indicate that intramitochondrial autonomy exists both with respect to their genesis and turnover. (M.G.B.)

  2. infarction in rats

    Directory of Open Access Journals (Sweden)

    Keyvan Yousefi

    2014-03-01

    Full Text Available Introduction: Nowadays, finding new therapeutic compounds from natural products for treatment and prevention of a variety of diseases including cardiovascular disorders is getting a great deal of attention. This approach would result in finding new drugs which are more effective and have fewer side effects than the conventional medicines. The present study was designed to investigate the anti-inflammatory effect of the methanolic extract of Marrubium vulgare, a popular traditional medicinal herb, on isoproterenol-induced myocardial infarction (MI in rat model. Methods: Male Wistar rats were assigned to 6 groups of control, sham, isoproterenol, and treatment with 10, 20, and 40 mg/kg/12h of the extract given orally concurrent with MI induction. A subcutaneous injection of isoproterenol (100 mg/kg/day for two consecutive days was used to induce MI. Then, histopathological changes and inflammatory markers were evaluated. Results: Isoproterenol injection increased inflammatory response, as shown by a significant increase in peripheral neutrophil count, myocardial myeloperoxidase (MPO activity and serum levels of creatinine kinase-MB (CK-MB and TNF-α (pM.vulgare extract serum CK-MB was subsided by 55.4%, 52.2% and 69%, respectively. Also treatment with the extract (40 mg/kg significantly reduced (p<0.001 MPO activity in MI group. The levels of TNF-α was also considerably declined in the serums of MI group (p<0.001. In addition, peripheral neutrophil count, was significantly lowered by all doses of the extract (p<0.001. Interstitial fibrosis significantly was attenuated in treated groups compared with control MI group.Conclusion:The results of study demonstrate that the M. vulgare extract has strong protective effects against isoproterenol-induced myocardial infarction and it seems possible that this protection is due to its anti-inflammatory effects.

  3. The thymus reconstituted nude rat

    DEFF Research Database (Denmark)

    Hougen, H P; Klausen, B

    1987-01-01

    The monoclonal antibodies OX6, OX19, W3/13, OX7, OX8, and W3/25 were used to gain information about the distribution of different lymphocyte subpopulations in peripheral lymphoid organs of neonatally isogeneic and allogeneic thymus reconstituted nude rats. Splenic mitogen responsiveness, xenogeneic...... cell response is far better following isografting. We, therefore, conclude that isogeneic thymus grafting is an easy method of reconstituting the nude rat immunologically....

  4. False Context Fear Memory in Rats

    Science.gov (United States)

    Bae, Sarah; Holmes, Nathan M.; Westbrook, R. Frederick

    2015-01-01

    Four experiments used rats to study false context fear memories. In Experiment 1, rats were pre-exposed to a distinctive chamber (context A) or to a control environment (context C), shocked after a delay in a second chamber (context B) and tested either in B or A. Rats pre-exposed to A froze just as much as control rats in B but more than control…

  5. EFFECT OF ETHANOL ON HEPATOBILIARY TRANSPORT OF CATIONIC DRUGS - A STUDY IN THE ISOLATED-PERFUSED RAT-LIVER, RAT HEPATOCYTES AND RAT MITOCHONDRIA

    NARCIS (Netherlands)

    STEEN, H; MEIJER, DKF; Merema, M.T.

    The effect of ethanol on the hepatic uptake of various cationic drugs was studied in isolated perfused rat livers, isolated rat hepatocytes and isolated rat liver mitochondria. In isolated rat hepatocytes and in isolated perfused rat livers, the uptake of the model organic cation

  6. Tuberculosis Detection by Giant African Pouched Rats

    Science.gov (United States)

    Poling, Alan; Weetjens, Bart; Cox, Christophe; Beyene, Negussie; Durgin, Amy; Mahoney, Amanda

    2011-01-01

    In recent years, operant discrimination training procedures have been used to teach giant African pouched rats to detect tuberculosis (TB) in human sputum samples. This article summarizes how the rats are trained and used operationally, as well as their performance in studies published to date. Available data suggest that pouched rats, which can…

  7. The serotonin transporter knockout rat : A review

    NARCIS (Netherlands)

    Olivier, Jocelien; Cools, Alexander; Ellenbroek, Bart A.; Cuppen, E.; Homberg, Judith; Kalueff, Allan V.; LaPorte, Justin L.

    2010-01-01

    This chapter dicusses the most recent data on the serotonin transporter knock-out rat, a unique rat model that has been generated by target-selected N-ethyl-N-nitrosourea (ENU) driven mutagenesis. The knock-out rat is the result of a premature stopcodon in the serotonin transporter gene, and the

  8. The rat GPRC6A

    DEFF Research Database (Denmark)

    Wellendorph, Petrine; Burhenne, Nicole; Christiansen, Bolette

    2007-01-01

    GPRC6A is a novel member of family C of G protein-coupled receptors with so far elusive biological function. GPRC6A has been described in human and mouse as a promiscuous l-alpha-amino acid receptor. We now report the cloning, expression analysis and, functional characterization of the rat...... orthologue of GPRC6A. Full-length cloning of rat GPRC6A (rGPRC6A) was accomplished using amplification of cDNA from taste tissue, and the identity of rGPRC6A confirmed at both the genomic and the protein level by similarity studies. Using selective primers, reverse transcriptase polymerase chain reaction...... conservation of GPRC6A to the rat and signifies the physiological importance and emerging pharmacological potential of GPRC6A....

  9. Phosphodiesterases in the rat ovary

    DEFF Research Database (Denmark)

    Petersen, Tonny Studsgaard; Stahlhut, Martin; Andersen, Claus Yding

    2015-01-01

    that augmented cAMP levels stimulate primordial follicle growth. The present study examined the gene expression, enzyme activity and immunolocalization of the different cAMP hydrolysing PDEs families in the rat ovary. Further, the effect of PDE4 inhibition on primordial follicle activation in cultured neonatal...... rat ovaries was also evaluated. We found varied expression of all eight families in the ovary with Pde7b and Pde8a having the highest expression each accounting for more than 20% of the total PDE mRNA. PDE4 accounted for 15-26% of the total PDE activity. Immunoreactive PDE11A was found in the oocytes...... and PDE2A in the corpora lutea. Incubating neonatal rat ovaries with PDE4 inhibitors did not increase primordial follicle activation or change the expression of the developing follicle markers Gdf9, Amh, Inha, the proliferation marker Mki67 or the primordial follicle marker Tmeff2. In addition, the c...

  10. Voluntary Sleep Loss in Rats

    Science.gov (United States)

    Oonk, Marcella; Krueger, James M.; Davis, Christopher J.

    2016-01-01

    Study Objectives: Animal sleep deprivation (SDEP), in contrast to human SDEP, is involuntary and involves repeated exposure to aversive stimuli including the inability of the animal to control the waking stimulus. Therefore, we explored intracranial self-stimulation (ICSS), an operant behavior, as a method for voluntary SDEP in rodents. Methods: Male Sprague-Dawley rats were implanted with electroencephalography/electromyography (EEG/EMG) recording electrodes and a unilateral bipolar electrode into the lateral hypothalamus. Rats were allowed to self-stimulate, or underwent gentle handling-induced SDEP (GH-SDEP), during the first 6 h of the light phase, after which they were allowed to sleep. Other rats performed the 6 h ICSS and 1 w later were subjected to 6 h of noncontingent stimulation (NCS). During NCS the individual stimulation patterns recorded during ICSS were replayed. Results: After GH-SDEP, ICSS, or NCS, time in nonrapid eye movement (NREM) sleep and rapid eye movement (REM) sleep increased. Further, in the 24 h after SDEP, rats recovered all of the REM sleep lost during SDEP, but only 75% to 80% of the NREM sleep lost, regardless of the SDEP method. The magnitude of EEG slow wave responses occurring during NREM sleep also increased after SDEP treatments. However, NREM sleep EEG slow wave activity (SWA) responses were attenuated following ICSS, compared to GH-SDEP and NCS. Conclusions: We conclude that ICSS and NCS can be used to sleep deprive rats. Changes in rebound NREM sleep EEG SWA occurring after ICSS, NCS, and GH-SDEP suggest that nonspecific effects of the SDEP procedure differentially affect recovery sleep phenotypes. Citation: Oonk M, Krueger JM, Davis CJ. Voluntary sleep loss in rats. SLEEP 2016;39(7):1467–1479. PMID:27166236

  11. Raynaud's Phenomenon: Revisiting a Rare Sign of Pheochromocytoma and Paraganglioma.

    Science.gov (United States)

    Patil, Virendra Ashokrao; Kasaliwal, Rajiv; Goroshi, Manjunath R; Lila, Anurag R; Bandgar, Tushar; Shah, Nalini S

    2017-08-01

    Paraganglioma (PGL) are rare tumors arising from extra-adrenal chromaffin cells and occasionally secret catecholamines. The patient commonly presents with headache, palpitation, anxiety, diaphoresis, and episodic or sustained hypertension. Rarely patient can present with Raynaud's phenomenon. We present a case of adolescent girl who presented with isolated Raynaud's phenomenon as only manifestation of metastasis of PGL 3 years after undergoing surgical excision of normetanephrine secreting abdominal PGL. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Pheochromocytoma and Paraganglioma: Current Functional and Future Molecular Imaging

    International Nuclear Information System (INIS)

    Blanchet, Elise M.; Martucci, Victoria; Pacak, Karel

    2012-01-01

    Paragangliomas are neural crest-derived tumors, arising either from chromaffin sympathetic tissue (in adrenal, abdominal, intra-pelvic, or thoracic paraganglia) or from parasympathetic tissue (in head and neck paraganglia). They have a specific cellular metabolism, with the ability to synthesize, store, and secrete catecholamines (although most head and neck paragangliomas do not secrete any catecholamines). This disease is rare and also very heterogeneous, with various presentations (e.g., in regards to localization, multifocality, potential to metastasize, biochemical phenotype, and genetic background). With growing knowledge, notably about the pathophysiology and genetic background, guidelines are evolving rapidly. In this context, functional imaging is a challenge for the management of paragangliomas. Nuclear imaging has been used for exploring paragangliomas for the last three decades, with MIBG historically as the first-line exam. Tracers used in paragangliomas can be grouped in three different categories. Agents that specifically target catecholamine synthesis, storage, and secretion pathways include: 123 and 131I-metaiodobenzylguanidine (123/131I-MIBG), 18F-fluorodopamine (18F-FDA), and 18F-fluorodihydroxyphenylalanine (18F-FDOPA). Agents that bind somatostatin receptors include 111In-pentetreotide and 68Ga-labeled somatostatin analog peptides (68Ga-DOTA-TOC, 68Ga-DOTA-NOC, 68Ga-DOTA-TATE). The non-specific agent most commonly used in paragangliomas is 18F-fluorodeoxyglucose (18F-FDG). This review will first describe conventional scintigraphic exams that are used for imaging paragangliomas. In the second part we will emphasize the interest in new PET approaches (specific and non-specific), considering the growing knowledge about genetic background and pathophysiology, with the aim of understanding how tumors behave, and optimally adjusting imaging technique for each tumor type.

  13. The Epidemiology of Pheochromocytoma: Increasing incidence and changing clinical presentation

    DEFF Research Database (Denmark)

    Ebbehoj, A; Søndergaard, Esben; Trolle, Christian

    2017-01-01

    (population 1.75 million).Incidence rates were calculated using Poisson regression and time trends were analysed with year as a continuous explanatory variable. As incidence increased significantly in 2007–2015, we compared the clinical characteristics of patients diagnosed in this time interval with patients...

  14. Pheochromocytoma (PC12 Cell Response on Mechanobactericidal Titanium Surfaces

    Directory of Open Access Journals (Sweden)

    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.

  15. Catecholamine-synthesizing enzymes in carcinoid tumors and pheochromocytomas

    NARCIS (Netherlands)

    Meijer, WG; Copray, SCVM; Hollema, H; Kema, IP; Zwart, N; Mantingh-Otter, [No Value; Links, TP; Willemse, PHB; de Vries, EGE

    Background: Serotonin is the principal endocrine product of carcinoid tumors, but simultaneously increased production of catecholamines has been described in these tumors. As it is not clear whether these tumors contain specific enzymes for catecholamine synthesis, we aimed to detect

  16. Emerging role of dopamine in neovascularization of pheochromocytoma and paraganglioma

    NARCIS (Netherlands)

    Osinga, Thamara E; Links, Thera P; Dullaart, Robin P F; Pacak, Karel; Horst-Schrivers, van der Anouk; Kerstens, Michiel N.; Kema, Ido P

    Dopamine is a catecholamine that acts both as a neurotransmitter and as a hormone, exerting its functions via dopamine (DA) receptors that are present in a broad variety of organs and cells throughout the body. In the circulation, DA is primarily stored in and transported by blood platelets.

  17. Case 214: Adrenal pheochromocytoma with perirenal brown fat stimulation.

    Science.gov (United States)

    Martínez-Sapiña Llanas, María José; Romeu Vilar, Daniel; Jorge Méndez, Segundo; Álvarez García, Augusto

    2015-02-01

    History A 61-year-old woman with well-controlled diabetes presented with a 10-year history of hypertension, stifling sensation, and flushing. Her body mass index was 19.1 kg/m(2) (normal range, 18.5-25.0 kg/m(2)). She was being followed up for mild hypercalcemia (calcium level, 10.8 mg/dL [2.7 mmol/L]) (normal range, 8.5-10.5 mg/dL [2.12-2.62 mmol/L]) by the endocrinologist (S.J.M.), who decided to perform a technetium 99m sestamibi ((99m)Tc MIBI) parathyroid scan. The test showed an abnormal tracer deposit in the region of the clavicle and sternum; thus, unenhanced thoracic computed tomography (CT) was performed. No mass was seen in the region of abnormality. In light of these findings, the patient underwent contrast material-enhanced (120 mL of iopromide, Ultravist 300; Schering, Berlin, Germany) thoracic abdominopelvic CT. There was no history of underlying malignancy, and the complete blood counts were normal. The axial and appendicular skeleton showed no sign of lesions.

  18. Pheochromocytomas and paragangliomas: from DNA to the daily clinical practice

    NARCIS (Netherlands)

    B-J. Petri (Bart-Jeroen)

    2010-01-01

    textabstractThe neuroendocrine system is a diffuse system in which the nervous system and the hormones of the endocrine glands interact. The neuroendocrine organs of the sympathetic and parasympathetic autonomic nervous system are called paraganglia. These organs usually manifest as anatomically

  19. Peculiarities of osteoarthritis in rats

    Directory of Open Access Journals (Sweden)

    Maria Drahulian

    2016-05-01

    Full Text Available Was received model of osteoarthritis in the rat line Wistar, by a one-time injection of CH3COOI acid into the knee joint. There changes in joint studied histological and clinical methods.On the 7-th day of the experiment was installed resemblance to similar changes in the joints of humans with acquired osteoarthritis

  20. Pagophagia in the albino rat.

    Science.gov (United States)

    Woods, S C; Weisinger, R S

    1970-09-25

    Pagophagia, or ice-eating, is a common symptom of iron-deficiency anemia in humans. Rats made anemic by withdrawal of blood consume a significantly greater proportion of their daily water in the form of ice than nonanemic controls. Recovery from the anemia eliminates the pagophagia.

  1. on gentamicin nephrotoxicity in rats

    African Journals Online (AJOL)

    Admin

    Design: Experimental study using a pre-validated model. Subject: Adult Swiss albino rats weighing 140-214g, Generic gentamicin sulphate ... antibiotics to clinical medicine in 1944 (Gilbert, 1991) heralded an era of triumph over gram negative pathogens and, previously disastrous, sepsis. Nephrotoxicity and ototoxicity are ...

  2. Tubuloglomerular feedback in Dahl rats

    DEFF Research Database (Denmark)

    Karlsen, F M; Leyssac, P P; Holstein-Rathlou, N H

    1998-01-01

    We have previously demonstrated a loss of autoregulation in Dahl salt-sensitive (Dahl-S) rats rendered hypertensive on a high-salt diet. To determine whether this was due to a decreased activity of either the myogenic or the tubuloglomerular feedback (TGF) response, we tested the TGF response...

  3. Acute renal failure in rats

    International Nuclear Information System (INIS)

    Cederholm, C.; Almen, T.; Bergquist, D.; Golman, K.; Takolander, R.; Malmoe Allmaenna Sjukhus

    1989-01-01

    It was demonstrated in rats that renal injury which follows transient renal hypoxia is potentiated by the contrast media metrizoate, ioxaglate, iopamidol and iohexol. Intravenous injection of 1 g I/kg of all four media alone to 82 rats caused no significant increase in serum urea 1, 3 and 7 days later. The percentage increase of serum urea is given in median values and interquartile range (in parentheses). Bilateral renal arterial occlusion alone for 40 minutes in 42 rats increased serum urea one day later by 40% (20-130). Intravenous injection of the media followed in one hour by bilateral renal arterial occlusion for 40 minutes in 104 rats caused serum urea to increase one day later by 130% (70-350) after metrizoate, by 220% (50-380) after ioxaglate, by 290 % (60-420) after iopamidol and by 160% (50-330) after iohexol. There were no significant differences between the potentiating effects of the various media on ischemic renal failure. (orig.)

  4. LOCOMOTOR DEVELOPMENT IN UNDERNOURISHED RATS

    NARCIS (Netherlands)

    GRAMSBERGEN, A; WESTERGA, J

    1992-01-01

    The effects of undernutrition on the development of locomotion were studied in fourteen rats. Mothers received about 40% of normal quantities of standard laboratory food from the 5th day of gestation until weaning at the 21st day after birth. Qualitative as well as quantitative aspects of locomotion

  5. Acute renal failure in rats

    International Nuclear Information System (INIS)

    Cederholm, C.; Almen, T.; Bergqvist, D.; Golman, K.; Takolander, R.

    1986-01-01

    Acute renal failure is a serious complication oif reconstructive aortoiliac surgery. The question was raised whether its etiology includes interaction between preoperative angiographic contrast medium and intra-operative clamping of the renal arteries. Renal arteries of 180 rats were bilaterally clamped 10 to 120 min and serum urea was determined from 3 h to 7 days later. In 35 rats 40 min clamping alone produced an increase in urea reaching a maximum 1 day later (median increase 70%). In 3 groups of 12 rats intravenous injection of the contrast medium metrizoate alone in doses 1, 2 and 3 g I/kg body-weight produced no significant increase in urea. Intravenous injection of the same doses to 3 groups of 10 rats each followed 1 h later by renal arterial occlusion for 40 min produced median urea increases one day later of 110, 130 and 170%, respectively, in the 3 groups. The increase was higher than that produced by contrast medium alone (p<0.01) or by renal artery clamping alone (p<0.05) indicating a potentiation of transient renal failure by the combination of contrast medium and renal arterial clamping. (orig.)

  6. August rats are more resistant to arrhythmogenic effect of myocardial ischemia and reperfusion than Wistar rats.

    Science.gov (United States)

    Belkina, L M; Kirillina, T N; Pshennikova, M G; Arkhipenko, Yu V

    2002-06-01

    As differentiated from Wistar rats, myocardial ischemia and reperfusion produce no ventricular fibrillation in August rats. Pretreatment with nitric oxide synthase inhibitor Nw-nitro-L-arginine increased mortality rate in August rats with acute myocardial infarction from 20 to 40%. Under these conditions mortality rate in Wistar rats increased from 50 to 71%. Interstrain differences in the resistance of these animals to the arrhythmogenic effect of ischemia are probably associated with higher activity of the nitric oxide system in August rats compared to Wistar rats.

  7. Diminished hormonal responses to exercise in trained rats

    DEFF Research Database (Denmark)

    Galbo, H; Richter, Erik; Holst, J J

    1977-01-01

    Male rats (120 g) either were subjected to a 12-wk physical training program (T rats) or were sedentary controls (C rats). Subsequently the rats were killed at rest or after a 45- or 90-min forced swim. At rest, T rats had higher liver and muscle glycogen concentrations but lower plasma insulin...

  8. Kangaroo rat bone compared to white rat bone after short-term disuse and exercise

    Science.gov (United States)

    Muths, E.; Reichman, O. J.

    1996-01-01

    Kangaroo rats (Dipodomys ordii) were used to study the effects of confinement on mechanical properties of bone with a long range objective of proposing an alternative to the white rat model for the study of disuse osteoporosis. Kangaroo rats exhibit bipedal locomotion, which subjects their limbs to substantial accelerative forces in addition to the normal stress of weight bearing. We subjected groups of kangaroo rats and white rats (Rattus norvegicus) to one of two confinement treatments or to an exercise regime; animals were exercised at a rate calculated to replicate their (respective) daily exercise patterns. White laboratory rats were used as the comparison because they are currently the accepted model used in the study of disuse osteoporosis. After 6 weeks of treatment, rats were killed and the long bones of their hind limbs were tested mechanically and examined for histomorphometric changes. We found that kangaroo rats held in confinement had less ash content in their hind limbs than exercised kangaroo rats. In general, treated kangaroo rats showed morphometric and mechanical bone deterioration compared to controls and exercised kangaroo rats appeared to have slightly “stronger” bones than confined animals. White rats exhibited no significant differences between treatments. These preliminary results suggest that kangaroo rats may be an effective model in the study of disuse osteoporosis.

  9. The thymus reconstituted nude rat

    DEFF Research Database (Denmark)

    Hougen, H P; Klausen, B

    1987-01-01

    The monoclonal antibodies OX6, OX19, W3/13, OX7, OX8, and W3/25 were used to gain information about the distribution of different lymphocyte subpopulations in peripheral lymphoid organs of neonatally isogeneic and allogeneic thymus reconstituted nude rats. Splenic mitogen responsiveness, xenogeneic...... skin rejection, and antibody titers were also measured in the same groups of animals. The experiments showed that both allogeneic and isogeneic thymus grafting cause a significant amplification of cells in the different T lymphocyte subpopulations. The functional tests, however, indicate that the T...... cell response is far better following isografting. We, therefore, conclude that isogeneic thymus grafting is an easy method of reconstituting the nude rat immunologically....

  10. Renal function in streptozotocin-diabetic rats

    DEFF Research Database (Denmark)

    Jensen, P K; Christiansen, J S; Steven, K

    1981-01-01

    Renal function was examined with micropuncture methods in the insulin-treated streptozotocin-diabetic rat. Kidney glomerular filtration rate was significantly higher in the diabetic rats (1.21 ml/min) than in the control group (0.84 ml/min) Nephron glomerular filtration rate increased in proportion...... to the rise in kidney glomerular filtration rate (diabetic rats: 37.0 nl/min; control rats: 27.9 nl/min). Likewise renal plasma flow was significantly higher in the diabetic rats (4.1 ml/min) than in the control group (3.0 ml/min). Glomerular capillary pressure was identical in both groups (56.0 and 56.0 mm......-1mmHg-1). Kidney weight was significantly higher in the diabetic rats (1.15 g; control rats: 0.96 g) while body weight was similar in both groups (diabetic rats: 232 g; control rats: 238 g). Calculations indicate that the increases in transglomerular hydraulic pressure, renal plasma flow...

  11. Renal alterations in prediabetic rats with periodontitis

    DEFF Research Database (Denmark)

    Andersen, Carla Cruvinel Pontes; Holmstrup, Palle; Buschard, Karsten

    2008-01-01

    BACKGROUND: Periodontitis was shown to have an impact on glucose levels in prediabetic and diabetic rats. The Zucker fatty rat (ZFR) is a well-characterized model of prediabetes presenting with impaired glucose tolerance, hyperinsulinemia, dyslipidemia, and moderate hypertension. The aim of the p......BACKGROUND: Periodontitis was shown to have an impact on glucose levels in prediabetic and diabetic rats. The Zucker fatty rat (ZFR) is a well-characterized model of prediabetes presenting with impaired glucose tolerance, hyperinsulinemia, dyslipidemia, and moderate hypertension. The aim...

  12. Characterization of rat lung ICAM-1

    DEFF Research Database (Denmark)

    Beck-Schimmer, B; Schimmer, R C; Schmal, H

    1998-01-01

    OBJECTIVE AND DESIGN: We expressed soluble rat ICAM-1, generated a polyclonal anti-ICAM-1 antibody, and studied ICAM-1 upregulation in lung inflammatory conditions. Bacterial and baculovirus expression systems were employed. MATERIAL: 250 g adult, male Long Evans rats were used. For in vitro...... studies, rat pulmonary artery endothelial cells (RPAEC), rat alveolar macrophages and aortic rings were stimulated (as described below) and evaluated for ICAM-1 expression. TREATMENT: RPAEC and macrophages were stimulated with lipopolysaccharide (LPS) and recombinant murine tumour necrosis factor alpha...

  13. X-ray lethality in diabetic rats

    International Nuclear Information System (INIS)

    Cember, H.; Thorson, T.M. Jr.

    1978-01-01

    Rats were made diabetic with streptozotocin and were irradiated with X-rays at various exposure levels in order to determine the LD-50/30 day dose. Non-diabetic control rats were exposed in a similar manner. The LD-50 exposures for the diabetic rats and the control rats were 436 R, and 617 R respectively. In view of the high prevalence of diabetes among the adult population, this finding may have important implications for diabetic workers who may be exposed accidentally to high levels of ionizing radiation

  14. Hyperparathyroidism is augmented by ovariectomy in Nagase analbuminemic rats.

    Science.gov (United States)

    Inaba, M; Morii, H; Katsumata, T; Goto, H; Ishimura, E; Kawagishi, T; Kamao, M; Okano, T; Nishizawa, Y

    2000-06-01

    The role of albumin in bone metabolism was studied in Nagase analbuminemic (NA) rats. Serum calcium (Ca), inorganic phosphate (Pi) and magnesium (Mg) concentrations did not differ between female NA and control Sprague-Dawley (SD) rats at the time of ovariectomy (ovx), although serum ionized Ca was significantly lower in NA rats than in SD rats. Serum parathyroid hormone (PTH) and osteocalcin (OC) concentrations and urinary Ca excretion were significantly greater in NA rats than in SD rats, suggesting hyperparathyroidism and the resultant enhanced bone turnover in NA rats. Paradoxically, ovx increased serum PTH and OC in NA rats but not in SD rats. Ovx-induced exacerbation of hyperparathyroidism was confirmed by significantly greater conversion of 25-hydroxyvitamin D to 1, 25-dihydroxyvitamin D in ovx NA rats even after normalization to vitamin D-binding protein. Bone mineral density (BMD) in proximal tibia increased similarly in a time-dependent manner in sham-operated NA and SD rats. However, ovx ablated the time-dependent increase of BMD in SD rats and significantly decreased BMD in NA rats by 2 wk after ovx, resulting in a significantly lower BMD in ovx NA rats than in ovx SD rats. In summary, NA rats, which are analbuminemic with compensatory increases in lipid and protein synthesis, developed hyperparathyroidism, possibly due to an increase in serum Pi and a reduction of ionized Ca, and ovx induced a greater BMD reduction in NA rats than in SD rats, probably by exacerbating hyperparathyroidism.

  15. Stevia preferences in Wistar rats.

    Science.gov (United States)

    Núñez Martínez, Paula; Argüelles Luis, Juan; Perillán Méndez, Carmen

    2016-11-01

    The Stevia rebaudiana plant is likely to become a major source of high-potency sweetener for the growing natural-food market. S. rebaudiana is the source of a number of sweet diterpenoid glycosides, but the major sweet constituents are rebaudioside A and stevioside. These two constituents have similar pharmacokinetic and metabolic profiles in rats and humans, and thus, studies carried out with either steviol glycoside are relevant to both. Other studies illustrate the diversity of voluntary sweet intake in mammals. This study was done using a series of two-bottle tests that compared a wide range of sweetener concentrations versus saccharin concentrations and versus water. Wistar rats displayed preferences for stevia extract and pure rebaudioside A solutions over water at a range of concentrations (0.001% to 0.3%), and their intake peak occurred at 0.1% concentration. They also preferred solutions prepared with a commercial rebaudioside A plus erythritol mixture to water, and their peak was at 2% concentration. The present study provides new information about the responses of Wistar rats to stevia compounds and commercial stevia products such as Truvia. These results could help with the appropriate dosage selection for focused behavioral and physiological studies on stevia.

  16. Pathophysiology of the Belgrade Rat

    Directory of Open Access Journals (Sweden)

    Tania eVeuthey

    2014-04-01

    Full Text Available The Belgrade rat is an animal model of Divalent Metal Transporter-1 (DMT1 deficiency. This strain originates from an X-irradiation experiment first reported in 1966. Since then, the Belgrade rat’s pathophysiology has helped to reveal the importance of iron balance and the role of DMT1. This review discusses our current understanding of iron transport homeostasis and summarizes molecular details of DMT1 function. We describe how studies of the Belgrade rat have revealed key roles for DMT1 in iron distribution to red blood cells as well as duodenal iron absorption. The Belgrade rat’s pathology has extended our knowledge of hepatic iron handling, pulmonary and olfactory iron transport as well as brain iron uptake and renal iron handling. For example, relationships between iron and manganese metabolism have been discerned since both are essential metals transported by DMT1. Pathophysiologic features of the Belgrade rat provide us with a unique and interesting animal model to understand iron homeostasis.

  17. Disappearance of 125I-labelled rat growth hormone in nephrectomized and sham operated rats

    International Nuclear Information System (INIS)

    Wallace, A.L.C.; Stacy, B.D.

    1975-01-01

    125 I-labelled rat growth hormone (GH) was injected i.v. into rats immediately after nephrectomy or a sham operation. Serial blood samples were then taken for 2 hr from an indwelling arterial cannula. The rates of removal of trichloracetic acid precipitable radioactivity and immunoreactive 125 I-GH were both significantly decreased in the nephrectomized rats. Polyacrylamide gel electrophoresis of plasma samples taken at 5 min and 120 min confirmed the observation that GH was removed from the circulation more slowly in the anephric rat. It is concluded that in the rat the kidney contributes significantly to the clearance of GH from the blood. (orig.) [de

  18. Modulation of rat behaviour by using a rat-like robot

    International Nuclear Information System (INIS)

    Shi, Qing; Ishii, Hiroyuki; Kinoshita, Shinichi; Takanishi, Atsuo; Okabayashi, Satoshi; Iida, Naritoshi; Kimura, Hiroshi; Shibata, Shigenobu

    2013-01-01

    In this paper, we study the response of a rat to a rat-like robot capable of generating different types of behaviour (stressful, friendly, neutral). Experiments are conducted in an open-field where a rat-like robot called WR-4 is put together with live rats. The activity level of each rat subject is evaluated by scoring its locomotor activity and frequencies of performing rearing (rising up on its hind limbs) and body grooming (body cuddling and head curling) actions, whereas the degree of preference of that is indicated by the robot–rat distance and the frequency of contacting WR-4. The moving speed and behaviour of WR-4 are controlled in real-time based on the feedback from rat motion. The activity level and degree of preference of rats for each experimental condition are analysed and compared to understand the influence of robot behaviour. The results of this study show that the activity level and degree of preference of the rat decrease when exposed to a stressful robot, and increase when the robot exhibit friendly behaviour, suggesting that a rat-like robot can modulate rat behaviour in a controllable, predictable way. (paper)

  19. Morphological and neurohistological changes in adolescent rats ...

    African Journals Online (AJOL)

    Pregnancy was confirmed and the pregnant rats were divided into 3 groups based on the 3 trimesters (A, B, C), with each group having a control and a treated subgroup. The Control Groups (A1, B1, ... offspring of tobacco smokers. Keywords: Cortex, Histology, Prenatal nicotine, Adolescent rats, Neurological abnormalities ...

  20. Costimulation and autoimmune diabetes in BB rats

    NARCIS (Netherlands)

    Beaudette-Zlatanova, BC; Whalen, B; Zipris, D; Yagita, H; Rozing, J; Groen, H; Benjamin, CD; Hunig, T; Drexhage, HA; Ansari, MJ; Leif, J; Mordes, JP; Greiner, DL; Sayegh, MH; Rossini, AA

    Costimulatory signals regulate T-cell activation. To investigate the role of costimulation in autoimmunity and transplantation, we studied the BB rat model of type 1 diabetes. Diabetes-prone BB (BBDP) rats spontaneously develop disease when 55-120 days of age. We observed that two anti-CD28

  1. stem bark in male Wistar rats

    African Journals Online (AJOL)

    Purpose: To investigate the acute and sub-acute toxicity effects of aqueous stem bark extract in male. Wistar rats. Methods: For the acute toxicity study, a single dose of 5000 mg/kg body weight of the extract was orally administered to the animals by oral gavage and the rats thereafter were observed for mortality and toxicity ...

  2. Attachment in rat pups, an experimental approach

    NARCIS (Netherlands)

    Gispen, W.H.; Sigling, H.; Engeland, H. van; Spruijt, B.M.

    1998-01-01

    John Bowlby's attachment theory states that attachment behavior has been strengthened throughout evolution as a consequence of its adaptive value. We investigated the presence of attachment-like behavior in rat pups, by offering a choice between the home nest and a same aged other nest. Rat pups

  3. Grooming behavior of spontaneously hypertensive rats

    NARCIS (Netherlands)

    Buuse, M. van den; Jong, Wybren de

    1987-01-01

    In an open field spontaneously hypertensive rats (SHR) exhibited lower scores for grooming when compared to their normotensive controls, the Wistar Kyoto rats (WKY). After i.c.v. injection of 1 μg ACTH1–24 cumulative 50-min grooming scores were lower in SHR. Analysis of subscores indicated that the

  4. Bromsulphalein (BSP) clearance in ageing rats

    NARCIS (Netherlands)

    Hollander, C.F.; Leeuw-Israel, F.R. de; Arp-Neefjes, J.M.

    1968-01-01

    Liver function in ageing rats was studied, using the bromsulphalein (BSP) clearance test. The test was done on ultramicro scale. This made it possible to repeat the test several times in the same animal and to start a longitudinal study. In 3-month-old rats the BSP retentions, measured 15, 30 and 45

  5. Experimental Salmonella typhimurium infections in rats. I

    DEFF Research Database (Denmark)

    Hougen, H P; Jensen, E T; Klausen, B

    1989-01-01

    The course of experimentally induced Salmonella typhimurium infection was studied in three groups of inbred LEW rats: homozygous +/+, athymic rnu/rnu and isogeneic thymus-grafted rnu/rnu rats. In the first experiment the animals were inoculated intraperitoneally with 10(8) bacteria and all animals...

  6. Metabolism of methylphenidate in dog and rat

    International Nuclear Information System (INIS)

    Egger, H.; Bartlett, F.; Dreyfuss, R.; Karliner, J.

    1981-01-01

    The urinary metabolites of methylphenidate in the dog and rat were investigated. After oral administration of 14C-labeled methylphenidate, approximately 86% and 63% of the dose was recovered in the urine of the dog and rat, respectively. Less than 1% of the dose was excreted as unchanged drug. Metabolism involved oxidation, hydrolysis, and conjugation processes. The primary hydrolytic product was alpha-phenyl-2-piperidineacetic acid (24%, dog; 35-40%, rat). The primary metabolites of oxidation were methyl 6-oxo-alpha-phenyl-2-piperidineacetate (3%, dog; 1.5%, rat) and the glucuronide of alpha-(p-hydroxyphenyl)-2-piperidineacetic acid (10%, rat). The former also underwent extensive biotransformation, including: 1) hydrolysis to the lactam acid (27%, dog; 7-10%, rat) and subsequent carboxylic acid O-glucuronidation (15%, dog); or 2) hydroxylation at the 5-position (1%, dog; 2%, rat) and subsequent hydrolysis (4%, dog; 15-17%, rat); or 3) 5-O-glucuronidation (12%, dog). Additional minor metabolites from methyl-6-oxo-alpha-phenyl-2-piperidineacetate were the phenolic O-glucuronide of methyl alpha-(p-hydroxyphenyl)-6-oxo-2-piperidineacetate (1%, dog), and the 4-O-glucuronide of methyl 4-hydroxy-6-oxo-alpha-phenyl-2-piperidineacetate (1%, dog), and the taurine amide conjugate of alpha-(p-hydroxyphenyl)-6-oxo-2-piperidineacetic acid (1%, dog). Additional products from methylphenidate conjugation included methyl 1-carbamoyl-alpha-phenyl-2-piperidineacetate (1%, dog or rat) and its carboxylic acid hydrolysis product (1%, rat). The chirality of the major metabolites isolated from dog urine showed that metabolism was partially stereoselective in all investigated cases, except in the formation of alpha-phenyl-2-piperidineacetic acid

  7. Mitochondrial DNA phylogeography of the Norway rat.

    Directory of Open Access Journals (Sweden)

    Ying Song

    Full Text Available Central Eastern Asia, foremost the area bordering northern China and Mongolia, has been thought to be the geographic region where Norway rats (Rattus norvegicus have originated. However recent fossil analyses pointed to their origin in southern China. Moreover, whereas analyses of fossils dated the species' origin as ∼ 1.2-1.6 million years ago (Mya, molecular analyses yielded ∼ 0.5-2.9 Mya. Here, to study the geographic origin of the Norway rat and its spread across the globe we analyzed new and all published mitochondrial DNA cytochrome-b (cyt-b; N = 156 and D-loop (N = 212 sequences representing wild rats from four continents and select inbred strains. Our results are consistent with an origin of the Norway rat in southern China ∼ 1.3 Mya, subsequent prehistoric differentiation and spread in China and Asia from an initially weakly structured ancestral population, followed by further spread and differentiation across the globe during historic times. The recent spreading occurred mostly from derived European populations rather than from archaic Asian populations. We trace laboratory strains to wild lineages from Europe and North America and these represent a subset of the diversity of the rat; leaving Asian lineages largely untapped as a resource for biomedical models. By studying rats from Europe we made the observation that mtDNA diversity cannot be interpreted without consideration of pest control and, possibly, the evolution of rodenticide resistance. However, demographic models explored by forward-time simulations cannot fully explain the low mtDNA diversity of European rats and lack of haplotype sharing with their source from Asia. Comprehensive nuclear marker analyses of a larger sample of Norway rats representing the world are needed to better resolve the evolutionary history of wild rats and of laboratory rats, as well as to better understand the evolution of anticoagulant resistance.

  8. blood pressure reducing effect of bitter kola in wistar rats

    African Journals Online (AJOL)

    DEAN'S OFFICE

    ABSTRACT: In this study the effect of Garcinia kola (GK) on blood pressure was investigated. Albino wistar rats were divided into three groups. Groups A rats had normal rat chow and water ad-libitum while groups B and C rats had Garcinia kola diet of 10% w/w and 15% w/w respectively, their blood pressures were ...

  9. Anxiolytic Treatment Impairs Helping Behavior in Rats.

    Science.gov (United States)

    Ben-Ami Bartal, Inbal; Shan, Haozhe; Molasky, Nora M R; Murray, Teresa M; Williams, Jasper Z; Decety, Jean; Mason, Peggy

    2016-01-01

    Despite decades of research with humans, the biological mechanisms that motivate an individual to help others remain poorly understood. In order to investigate the roots of pro-sociality in mammals, we established the helping behavior test, a paradigm in which rats are faced with a conspecific trapped in a restrainer that can only be opened from the outside. Over the course of repeated test sessions, rats exposed to a trapped cagemate learn to open the door to the restrainer, thereby helping the trapped rat to escape (Ben-Ami Bartal et al., 2011). The discovery of this natural behavior provides a unique opportunity to probe the motivation of rodent helping behavior, leading to a deeper understanding of biological influences on human pro-sociality. To determine if an affective response motivates door-opening, rats receiving midazolam, a benzodiazepine anxiolytic, were tested in the helping behavior test. Midazolam-treated rats showed less helping behavior than saline-treated rats or rats receiving no injection. Yet, midazolam-treated rats opened a restrainer containing chocolate, highlighting the socially specific effects of the anxiolytic. To determine if midazolam interferes with helping through a sympatholytic effect, the peripherally restricted beta-adrenergic receptor antagonist nadolol was administered; nadolol did not interfere with helping. The corticosterone response of rats exposed to a trapped cagemate was measured and compared to the rats' subsequent helping behavior. Rats with the greatest corticosterone responses showed the least helping behavior and those with the smallest responses showed the most consistent helping at the shortest latency. These results are discussed in terms of their implications for the interaction between stress and pro-social behavior. Finally, we observed that door-opening appeared to be reinforcing. A novel analytical tool was designed to interrogate the pattern of door-opening for signs that a rat's behavior on one session

  10. Oxidative stress of crystalline lens in rat menopausal model

    OpenAIRE

    Acer, Semra; Pekel, Gökhan; Küçükatay, Vural; Karabulut, Aysun; Yağcı, Ramazan; Çetin, Ebru Nevin; Akyer, Şahika Pınar; Şahin, Barbaros

    2016-01-01

    ABSTRACT Purpose: To evaluate lenticular oxidative stress in rat menopausal models. Methods: Forty Wistar female albino rats were included in this study. A total of thirty rats underwent oophorectomy to generate a menopausal model. Ten rats that did not undergo oophorectomy formed the control group (Group 1). From the rats that underwent oophorectomy, 10 formed the menopause control group (Group 2), 10 were administered a daily injection of methylprednisolone until the end of the study (Gro...

  11. Electroencephalographic changes in albino rats subjected to stress

    Science.gov (United States)

    Mercier, J.; Assouline, G.; Fondarai, J.

    1980-01-01

    Twenty one albino Wistar rats were subjected to stress for 7 hours. There was a significant difference in the slopes of regression lines for 7 nonulcerous rats and those for 14 ulcerous rats. Nonulcerous rats subjected to stress showed greater EEG curve synchronization than did ulcerous rats. If curve synchronization can be equated to a relaxed state, it may therefore be possible to explain the protective action of hypnotics, tranquilizers and analgesics on ulcers.

  12. Epidermal growth factor reactivity in rat milk

    DEFF Research Database (Denmark)

    Raaberg, Lasse; Nexø, Ebba; Tollund, L

    1990-01-01

    The concentration of EGF immunoreactivity in rat whey increases from 0.3 pmol/ml at lactation day 1 to 2.0 pmol/ml at lactation day 19. The concentration of EGF is not influenced when the rats undergo sialoadenectomy prior to mating. On S-200 gel chromatography, almost all EGF-reactivity in rat...... whey elutes as a broad peak corresponding to a Stokes radius of 4.0 nm (an approximate molecular weight of 80 kDa). Almost no 6 kDa EGF is present. Judged by gel filtration of whey pre-incubated with 125I-EGF (6 kDa), no binding protein for EGF is present in rat whey. When rat milk is incubated...... in rat whey behaves as a peptide with a Stokes radius of 2.7 nm, corresponding to a molecular weight of approximately 35 kDa at gel filtration. Comparative binding studies between EGF purified from the submandibular glands and the EGF purified from rat whey confirm differences in the binding...

  13. Total parenteral nutrition in diabetic rats

    International Nuclear Information System (INIS)

    Norcross, E.D.; Stein, T.P.

    1986-01-01

    Parenteral Nutrition with hypertonic glucose is frequently given to diabetic patients. Large amounts of insulin can be required. The purpose of this investigation was to develop a totally parenterally nourished diabetic rat model. 200 g Female Sprague Dawley rats were made diabetic by i.v. injection of streptozotocin (50 mg/kg). Rats were then allowed to recover for at least 1 week before undergoing surgical insertion of a central venous catheter for parenteral feeding. TPN was begun 3 days after surgery. Prior to this they were allowed unlimited access to food and water. Control (non-streptozotocin treated) rats were run at the same time. Protein turnover was investigated by using 15 N glycine. Preliminary results: diabetic rats given mostly fat as a calorie source survived well in the absence of exogenous insulin whereas those that were given glucose only as their non-protein calorie source showed poor survival even with exogenous insulin. N balance and protein turnover in the lipid treated diabetic rats were comparable to the non-diabetic control rats

  14. Toxicity of aluminum given to rats

    International Nuclear Information System (INIS)

    Katoh, Y.; Gotoh, Y.; Yamamoto, K.; Daimon, T.

    2001-01-01

    Aluminum nitrilotriacetate (A1-NTA) is given intraperitoneally five times to rats groups at the rate of 5 mgAl/kg/week. A rats group to which only chelating agent, nitriloacetate (NTA) is given, and a reference rats group are kept over five weeks, also. Element concentrations of Al, Ca, Cl, Cu, K, Mg, Mn, and Na localized on the internal organs of the rats groups, such as brain, bone, kidney, and liver, are measured by neutron activation analysis and proton-induced x-ray emission analysis (PIXE). A part of kidney and thighbone of the rats are observed and analyzed by a scanning electron microscopy for investigation of super-fine structure of the tissue. Increases of body weight of each the rats groups are measured at every week and compared with that of the reference group. The body weight of the rats group, to which only the Al-NTA is given, reduces significantly by comparison with the reference group and the group to which only the NTA is given. The kidneys of the Al-NTA group are hypertrophied and develop symptoms of nephritis. It is clear that the Al-NTA is dangerous to kidney, although only the NTA is not dangerous. Bone formation lesions are observed at the thighbone of the Al-NTA group. The paper discusses on the toxicity of the AL-NTA in detail. (M. Suetake)

  15. Autoprotection in acetaminophen intoxication in rats

    DEFF Research Database (Denmark)

    Dalhoff, K; Laursen, H; Bangert, K

    2001-01-01

    Autoprotection by acetaminophen, i.e. increased resistance to toxic effects caused by pretreatment, is a well-known phenomenon. The purpose of the present work was to identify mechanisms for increased acetaminophen tolerance induced by pretreatment of rats. One group of female Wistar rats...... (pretreated rats) received acetaminophen orally in increasing doses (1 to 4.3 g/kg) twice a week for 3 weeks, one group (naïve rats) received the vehicle. At time zero pretreated rats received a toxic dose of 7.5 g/kg (100% lethal in naïve rats), and naïve rats received a toxic dose of 4.3 g/kg. Blood...... and liver tissue were collected before and 12, 24, 36, and 48 hr after the toxic dose and were analysed for hepatic glutathione and cysteine contents, hepatic glutathione-S-transferase and blood alanine aminotransferase activity, as well as acetaminophen concentration in plasma. Steady-state mRNA levels...

  16. Ca{sup 2+}/calmodulin-dependent protein kinase phosphatase (CaMKP/PPM1F) interacts with neurofilament L and inhibits its filament association

    Energy Technology Data Exchange (ETDEWEB)

    Ozaki, Hana [Laboratory of Molecular Brain Science, Graduate School of Integrated Arts and Sciences, Hiroshima University, Higashi-Hiroshima, 739-8521 (Japan); Katoh, Tsuyoshi [Department of Biochemistry, Asahikawa Medical University, Asahikawa, 078-8510 (Japan); Nakagawa, Ryoko; Ishihara, Yasuhiro [Laboratory of Molecular Brain Science, Graduate School of Integrated Arts and Sciences, Hiroshima University, Higashi-Hiroshima, 739-8521 (Japan); Sueyoshi, Noriyuki; Kameshita, Isamu [Department of Life Sciences, Faculty of Agriculture, Kagawa University, Kagawa, 761-0795 (Japan); Taniguchi, Takanobu [Department of Biochemistry, Asahikawa Medical University, Asahikawa, 078-8510 (Japan); Hirano, Tetsuo; Yamazaki, Takeshi [Laboratory of Molecular Brain Science, Graduate School of Integrated Arts and Sciences, Hiroshima University, Higashi-Hiroshima, 739-8521 (Japan); Ishida, Atsuhiko, E-mail: aishida@hiroshima-u.ac.jp [Laboratory of Molecular Brain Science, Graduate School of Integrated Arts and Sciences, Hiroshima University, Higashi-Hiroshima, 739-8521 (Japan)

    2016-09-02

    Ca{sup 2+}/calmodulin-dependent protein kinase phosphatase (CaMKP/PPM1F) is a Ser/Thr phosphatase that belongs to the PPM family. Growing evidence suggests that PPM phosphatases including CaMKP act as a complex with other proteins to regulate cellular functions. In this study, using the two-dimensional far-western blotting technique with digoxigenin-labeled CaMKP as a probe, in conjunction with peptide mass fingerprinting analysis, we identified neurofilament L (NFL) as a CaMKP-binding protein in a Triton-insoluble fraction of rat brain. We confirmed binding of fluorescein-labeled CaMKP (F-CaMKP) to NFL in solution by fluorescence polarization. The analysis showed that the dissociation constant of F-CaMKP for NFL is 73 ± 17 nM (n = 3). Co-immunoprecipitation assay using a cytosolic fraction of NGF-differentiated PC12 cells showed that endogenous CaMKP and NFL form a complex in cells. Furthermore, the effect of CaMKP on self-assembly of NFL was examined. Electron microscopy revealed that CaMKP markedly prevented NFL from forming large filamentous aggregates, suggesting that CaMKP-binding to NFL inhibits its filament association. These findings may provide new insights into a novel mechanism for regulating network formation of neurofilaments during neuronal differentiation. - Highlights: • NFL was identified as a CaMKP-binding protein in an insoluble fraction of rat brain. • CaMKP bound to NFL in solution with a K{sub d} value of 73 ± 17 nM. • A CaMKP-NFL complex was found in NGF-differentiated PC12 cells. • CaMKP-binding to NFL inhibited its filament association. • CaMKP may regulate network formation of neurofilaments in neurons.

  17. Fetal rat pancreas transplantation in BB rats: immunohistochemical and functional evaluation

    DEFF Research Database (Denmark)

    Yderstræde, Knud Bonnet; Starklint, Henrik; Steinbrüchel, Daniel Andreas

    1993-01-01

    Spontaneously diabetic BB/Wor rats received either a syngeneic fetal pancreas transplant or adult islets. In the former, 4-8 fetal pancreases were transplanted, and in the latter, 3-5000 islets. Transplantation was performed by transferring a blood clot containing the pancreases or islets...... to the renal subcapsular space. Insulin therapy was undertaken postoperatively, except in one experiment with adult islets. Of the fetal pancreas transplanted BB rats, 52% became normoglycaemic, and 21% remained so throughout an observation period of 10 months. Nephrectomy caused a prompt return of diabetes....... The histological appearance of the grafts transplanted to the diabetic animals closely resembled that of grafts transplanted to normal rats in a parallel series. For comparison a group of BB rats received a syngeneic transplant of isolated adult islets from WF rats or BBW rats. Following adult islet...

  18. Antidepressant effect of taurine in diabetic rats.

    Science.gov (United States)

    Caletti, Greice; Olguins, Danielly B; Pedrollo, Elis F; Barros, Helena M T; Gomez, Rosane

    2012-10-01

    Clinical and preclinical studies have shown that diabetic individuals present more depressive behaviors than non-diabetic individuals. Taurine, one of the most abundant free amino acids in the central nervous system, modulates a variety of biological functions and acts as an agonist at GABAA receptors. Our objective was to assess the antidepressant effect of taurine in diabetic rats. Additionally, we studied the effect of taurine on weight gain, water and food intake, and blood glucose levels in diabetic and non-diabetic rats. Male Wistar rats were divided into control (CTR) and streptozotocin-induced diabetic (STZ) groups and were administered daily 0, 25, 50 or 100 mg/kg of taurine (n = 10 per subgroup) intraperitoneally. After 28 days of treatment, the animals were exposed to the forced swimming test, and their behaviors were recorded. Weight gain, water and food intake, and blood glucose levels were measured weekly. Our results showed that STZ rats had a higher immobility duration than CTR rats, and taurine decreased this depressive-like behavior in STZ rats at doses of 25 and 100 mg/kg. Both of these doses of taurine also decreased water intake and improved weight gain in STZ rats. All doses of taurine decreased the water intake in CTR rats. Taurine, at a dose of 100 mg/kg, decreased food intake and blood glucose levels in STZ rats. Because taurine is a GABA agonist and both amino acids are lower in the plasma of diabetic and depressive individuals, we hypothesize that taurine may represent a new adjuvant drug for the treatment of depression in diabetic individuals.

  19. Abdominal respiratory motor pattern in the rat.

    Science.gov (United States)

    Iizuka, Makito

    2010-01-01

    In this brief review, I focused on the abdominal expiratory motor pattern in the rat. In the vagotomized adult rat, hypercapnic acidosis evoked two patterns of the abdominal expiratory activity; one with low amplitude expiratory discharge (E-all activity) that persisted throughout the expiratory phase, and another with late expiratory and high amplitude bursts (E2 activity) superimposed on the E-all activity. The E-all activity appeared from milder acidosis than the E2 activity. In the anesthetized, vagotomized or vagus-intact neonatal rats, abdominal muscles often showed not only E2 activity but also a smaller additional burst occurred just after the termination of diaphragmatic inspiratory activity (E1 activity). Since this E1 activity is rarely observed in the adult rat, the abdominal respiratory motor pattern likely changes during postnatal development. Under light anesthesia, vagal afferent feedback shortened the respiratory cycle period due to shortening of the expiratory duration. Further decrement in depth of anesthesia changed the biphasic E2+E1 abdominal motor activity pattern to E-all activity pattern in the vagus-intact neonatal rat. Since this E-all activity was typically observed with short cycle period in the vagus-intact neonatal rat, relation with the E-all activity in the vagotomized adult rat remained unknown. The vagal feedback should have roles not only in setting the cycle period short but also shaping the expiratory motor pattern in the neonatal rat. Although abdominal muscles in the in vitro preparation from neonatal rat also showed biphasic E2+E1 activity, E2 activity was shorter and/or smaller than the E1 activity.

  20. Electrocardiography in rats: a comparison to human.

    Science.gov (United States)

    Konopelski, P; Ufnal, M

    2016-11-23

    Electrocardiography (ECG) in rats is a widely applied experimental method in basic cardiovascular research. The technique of ECG recordings is simple; however, the interpretation of electrocardiographic parameters is challenging. This is because the analysis may be biased by experimental settings, such as the type of anesthesia, the strain or age of animals. Here, we aimed to review electrocardiographic parameters in rats, their normal range, as well as the effect of experimental settings on the parameters variation. Furthermore, differences and similarities between rat and human ECG are discussed in the context of translational cardiovascular research.

  1. Cerebrovascular gene expression in spontaneously hypertensive rats

    DEFF Research Database (Denmark)

    Grell, Anne-Sofie; Frederiksen, Simona Denise; Edvinsson, Lars

    2017-01-01

    in the middle cerebral arteries from hypertensive compared to normotensive rats. The gene expression of 72 genes was decreased and the gene expression of 97 genes was increased. The following genes with a fold difference ≥1.40 were verified by quantitative PCR; Postn, Olr1, Fas, Vldlr, Mmp2, Timp1, Serpine1......, Mmp11, Cd34, Ptgs1 and Ptgs2. The gene expression of Postn, Olr1, Fas, Vldlr, Mmp2, Timp1 and Serpine1 and the protein expression of LOX1 (also known as OLR1) were significantly increased in the middle cerebral arteries from spontaneously hypertensive rats compared to Wistar-Kyoto rats. In conclusion...

  2. Noise Induces Oxidative Stress in Rat

    OpenAIRE

    Demirel, Reha; Mollaoğlu, Hakan; Yeşilyurt, Hasan; Üçok, Kağan; Ayçiçek, Abdullah; Akkaya, Muzaffer; Genç, Abdurrahman; Uygur, Ramazan; Doğan, Mevlüt

    2009-01-01

    Aim: Noise is described as disturbing and unwanted sound. In this study, we aimed to investigate the effect of noise on oxidative stress parameters in rat.Methods: Twenty male Sprague-Dawley rats were used in the study. Noise group (n=10) was exposed to noise for 20 days / 4 hour 100 dB. Control group (n=10) that was not exposed to any noise and was kept from any stress source, was hold in the same conditions. Baseline and after 20th day of the experiment, blood samples of rats were collected...

  3. Establishment of a novel dwarf rat strain: cartilage calcification insufficient (CCI) rats

    Science.gov (United States)

    TANAKA, Masami; WATANABE, Minoru; YOKOMI, Izuru; MATSUMOTO, Naoki; SUDO, Katsuko; SATOH, Hitoshi; IGARASHI, Tsuneo; SEKI, Azusa; AMANO, Hitoshi; OHURA, Kiyoshi; RYU, Kakei; SHIBATA, Shunichi; NAGAYAMA, Motohiko; TANUMA, Jun-ichi

    2014-01-01

    Rats with dwarfism accompanied by skeletal abnormalities, such as shortness of the limbs, tail, and body (dwarf rats), emerged in a Jcl-derived Sprague-Dawley rat colony maintained at the Institute for Animal Experimentation, St. Marianna University Graduate School of Medicine. Since the dwarfism was assumed to be due to a genetic mutation based on its frequency, we bred the dwarf rats and investigated their characteristics in order to identify the causative factors of their phenotypes and whether they could be used as a human disease model. One male and female that produced dwarf progeny were selected, and reproduction was initiated by mating the pair. The incidence of dwarfism was 25.8% among the resultant litter, and dwarfism occurred in both genders, suggesting that it was inherited in an autosomal recessive manner. At 12 weeks of age, the body weights of the male and female dwarf rats were 40% and 57% of those of the normal rats, respectively. In soft X-ray radiographic and histological examinations, shortening and hypoplasia of the long bones, such as the tibia and femur, were observed, which were suggestive of endochondral ossification abnormalities. An immunohistochemical examination detected an aggrecan synthesis disorder, which might have led to delayed calcification and increased growth plate thickening in the dwarf rats. We hypothesized that the principal characteristics of the dwarf rats were systemically induced by insufficient cartilage calcification in their long bones; thus, we named them cartilage calcification insufficient (CCI) rats. PMID:25736479

  4. Establishment of a novel dwarf rat strain: cartilage calcification insufficient (CCI) rats.

    Science.gov (United States)

    Tanaka, Masami; Watanabe, Minoru; Yokomi, Izuru; Matsumoto, Naoki; Sudo, Katsuko; Satoh, Hitoshi; Igarashi, Tsuneo; Seki, Azusa; Amano, Hitoshi; Ohura, Kiyoshi; Ryu, Kakei; Shibata, Shunichi; Nagayama, Motohiko; Tanuma, Jun-ichi

    2015-01-01

    Rats with dwarfism accompanied by skeletal abnormalities, such as shortness of the limbs, tail, and body (dwarf rats), emerged in a Jcl-derived Sprague-Dawley rat colony maintained at the Institute for Animal Experimentation, St. Marianna University Graduate School of Medicine. Since the dwarfism was assumed to be due to a genetic mutation based on its frequency, we bred the dwarf rats and investigated their characteristics in order to identify the causative factors of their phenotypes and whether they could be used as a human disease model. One male and female that produced dwarf progeny were selected, and reproduction was initiated by mating the pair. The incidence of dwarfism was 25.8% among the resultant litter, and dwarfism occurred in both genders, suggesting that it was inherited in an autosomal recessive manner. At 12 weeks of age, the body weights of the male and female dwarf rats were 40% and 57% of those of the normal rats, respectively. In soft X-ray radiographic and histological examinations, shortening and hypoplasia of the long bones, such as the tibia and femur, were observed, which were suggestive of endochondral ossification abnormalities. An immunohistochemical examination detected an aggrecan synthesis disorder, which might have led to delayed calcification and increased growth plate thickening in the dwarf rats. We hypothesized that the principal characteristics of the dwarf rats were systemically induced by insufficient cartilage calcification in their long bones; thus, we named them cartilage calcification insufficient (CCI) rats.

  5. Comparison of neurons derived from mouse P19, rat PC12 and human SH-SY5Y cells in the assessment of chemical- and toxin-induced neurotoxicity.

    Science.gov (United States)

    Popova, Dina; Karlsson, Jessica; Jacobsson, Stig O P

    2017-06-05

    Exposure to chemicals might be toxic to the developing brain. There is a need for simple and robust in vitro cellular models for evaluation of chemical-induced neurotoxicity as a complement to traditional studies on animals. In this study, neuronally differentiated mouse embryonal carcinoma P19 cells (P19 neurons) were compared with human neuroblastoma SH-SY5Y cells and rat adrenal pheochromocytoma PC12 cells for their ability to detect toxicity of methylmercury (MeHg), okadaic acid and acrylamide. Retinoic acid-treated P19 and SH-SY5Y cells and nerve growth factor-stimulated PC12 cells, allowed to differentiate for 6 days, were exposed to MeHg, okadaic acid and acrylamide for 48 h. Cell survival and neurite outgrowth were assessed with the calcein-AM assay and fluorescence detection of antibodies against the cytoskeletal neuron-specific protein βIII-tubulin, respectively. The effects of glutathione (GSH) and the potent inhibitor of GSH synthesis buthionine sulfoximine (BSO) on the MeHg induced-toxicity were assessed using the PrestoBlue™ cell viability assay and the TMRE mitochondrial membrane potential assay. Differentiated P19 cells developed the most extensive neuronal network among the three cell models and were the most sensitive neuronal model to detect neurotoxic effects of the test compounds. MeHg produced a concentration-dependent toxicity in differentiated P19 cells and SH-SY5Y cells, with statistically significant effects at concentrations from 0.1 μM in the P19 neurons and 1 μM in the SH-SY5Y cells. MeHg induced a decrease in the cellular metabolic activity and mitochondrial membrane potential (ΔΨm) in the differentiated P19 cells and SH-SY5Y cells, that were attenuated by GSH. Okadaic acid and acrylamide also showed statistically significant toxicity in the P19 neurons, but not in the SH-SY5Y cells or the P12 cells. P19 neurons are more sensitive to detect cytotoxicity of MeHg, okadaic acid and acrylamide than retinoic acid-differentiated SH

  6. Experimental Salmonella typhimurium infections in rats. I

    DEFF Research Database (Denmark)

    Hougen, H P; Jensen, E T; Klausen, B

    1989-01-01

    The course of experimentally induced Salmonella typhimurium infection was studied in three groups of inbred LEW rats: homozygous +/+, athymic rnu/rnu and isogeneic thymus-grafted rnu/rnu rats. In the first experiment the animals were inoculated intraperitoneally with 10(8) bacteria and all animals...... became severely septicemic and died within a week of inoculation, irrespective of presence or absence of thymus. In the second experiment the animals were inoculated with 10(6) bacteria, and both euthymic and thymus-grafted animals responded with high titres of anti bacterial antibodies while these were...... very low in the athymic nude animals. Polyclonal antibody production was only observed in the euthymic animals and only regarding IgG. Athymic rats were not able to clear the infection, while the thymus-grafted animals reacted like euthymic rats: Very few animals housed the bacteria four weeks after...

  7. Epidermal growth factor in the rat prostate

    DEFF Research Database (Denmark)

    Tørring, Niels; Jørgensen, P E; Poulsen, Steen Seier

    1998-01-01

    Epidermal growth factor (EGF) induces proliferation in prostate epithelial and stromal cells in primary culture. This investigation was set up to characterize the time and spatial expression of EGF in the rat prostate....

  8. Reactive Protein Synthesis in Pregnant Rats

    African Journals Online (AJOL)

    olayemitoyin

    /kg) groups. At terminal gestation day (GD) ranging from 0-20, the rats were sacrificed, and blood samples and amniotic fluids were collected. Thyroid hormone, C-reactive protein (CRP) and leptin assay was carried using the blood samples.

  9. Tissue disposition of bifenthrin in the rat

    Data.gov (United States)

    U.S. Environmental Protection Agency — Tissue disposition of bifenthrin in the rat and oral and intravenous administration. This dataset is associated with the following publication: Hughes , M., D. Ross...

  10. Rat sperm motility analysis: methodologic considerations

    Science.gov (United States)

    The objective of these studies was to optimize conditions for computer-assisted sperm analysis (CASA) of rat epididymal spermatozoa. Methodologic issues addressed include sample collection technique, sampling region within the epididymis, type of diluent medium used, and sample c...

  11. Black ginseng extract ameliorates hypercholesterolemia in rats

    Directory of Open Access Journals (Sweden)

    Evelyn Saba

    2016-04-01

    Conclusion: Administration of BG extracts to Sprague Dawley rats fed with high-cholesterol diet ameliorated hypercholesterolemia, which was mediated via modulation of cholesterol-metabolizing marker genes. This data throw a light on BG's cardioprotective effects.

  12. Cadmium induced nephrotoxicity in rats.

    Science.gov (United States)

    Lall, S B; Das, N; Rama, R; Peshin, S S; Khattar, S; Gulati, K; Seth, S D

    1997-02-01

    Onset of hypertension and nephropathy after 1,2, and 4 weeks of exposure to cadmium chloride (1 mg/kg, ip) was studied in rats by measuring changes in blood pressure and renal function (urinary output, electrolytes, serum creatinine, inulin clearance and Na+K+ ATPase). Significant decrease in body weight and rise in blood pressure were observed as early as one week of exposure while microalbuminuria was detected in 50% of the animals after 2 weeks. Na+K+ ATPase, a renal tubular enzyme, was depressed after 1 week with maximum lowering occurring after 4 weeks. There were no detectable changes in fluid intake, urine output, electrolytes, inulin clearance and serum creatinine even after 4 weeks. It is concluded that hypertension and tubular lesion set in earlier than glomerulopathy as indicated by microalbuminuria and the latter could be the consequence of rise in blood pressure.

  13. How rats combine temporal cues.

    Science.gov (United States)

    Guilhardi, Paulo; Keen, Richard; MacInnis, Mika L M; Church, Russell M

    2005-05-31

    The procedures for classical and operant conditioning, and for many timing procedures, involve the delivery of reinforcers that may be related to the time of previous reinforcers and responses, and to the time of onsets and terminations of stimuli. The behavior resulting from such procedures can be described as bouts of responding that occur in some pattern at some rate. A packet theory of timing and conditioning is described that accounts for such behavior under a wide range of procedures. Applications include the food searching by rats in Skinner boxes under conditions of fixed and random reinforcement, brief and sustained stimuli, and several response-food contingencies. The approach is used to describe how multiple cues from reinforcers and stimuli combine to determine the rate and pattern of response bouts.

  14. Tritium metabolism in rat tissues

    International Nuclear Information System (INIS)

    Takeda, H.

    1982-01-01

    As part of a series of studies designed to evaluate the relative radiotoxicity of various tritiated compounds, metabolism of tritium in rat tissues was studied after administration of tritiated water, leucine, thymidine, and glucose. The distribution and retention of tritium varied widely, depending on the chemical compound administered. Tritium introduced as tritiated water behaved essentially as body water and became uniformly distributed among the tissues. However, tritium administered as organic compounds resulted in relatively high incorporation into tissue constituents other than water, and its distribution differed among the various tissues. Moreover, the excretion rate of tritium from tissues was slower for tritiated organic compounds than for tritiated water. Administrationof tritiated organic compounds results in higher radiation doses to the tissues than does administration of tritiated water. Among the tritiated compounds examined, for equal radioactivity administered, leucine gave the highest radiation dose, followed in turn by thymidine, glucose, and water. (author)

  15. Rat growth during chronic centrifugation

    Science.gov (United States)

    Pitts, G. C.; Oyama, J.

    1978-01-01

    Female weanling rats were chronically centrifuged at 4.15 G with controls at terrestrial gravity. Samples were sacrificed for body composition studies at 0, 28, 63, 105 and 308 days of centrifugation. The centrifuged group approached a significantly lower mature body mass than the controls (251 and 318g) but the rate of approach was the same in both groups. Retirement to 1G on the 60th day resulted in complete recovery. Among individual components muscle, bone, skin, CNS, heart, kidneys, body water and body fat were changed in the centrifuged group. However, an analysis of the growth of individual components relative to growth of the total fat-free compartment revealed that only skin (which increased in mass) was responding to centrifugation per se.

  16. Properties of Flicker ERGs in Rat Models with Retinal Degeneration.

    Science.gov (United States)

    An, Jing; Guo, Qun; Li, Li; Zhang, Zuoming

    2012-01-01

    Purpose. To describe the characteristics of rod and cone functions in rat models for congenital stationary night blindness (CSNB) and retinal cone dysfunction (RCD). Methods. Rod and cone function were isolated by recording the rod-/cone-driven flicker and blue light flicker electroretinograms (ERGs). Results. During dark adaptation, the amplitudes of flicker ERGs in CSNB rats were lower than those in control rats; the responses of RCD rats were similar to control rats. During light adaptation, the amplitudes of flicker ERGs in CSNB rats were reduced; whereas the responses of RCD rats were not detected. Blue flicker ERGs were not observed in CSNB rats at lower frequencies. The cone driven critical flicker frequencies (CFFs) in control rats were 62 Hz. The rod driven CFF of RCD rats was 20 Hz; whereas the rod-/cone-driven CFF of CSNB rats both were about 25 Hz. Conclusions. The function of the rod system was damaged completely, the cones were the source of vision in CSNB rats. Rod system function is excellent in RCD rat. The rods of albinism rats are sensitive to frequencies less than 20 Hz; whereas the cones are sensitive to frequencies up to 62 Hz.

  17. Anxiolytic Treatment Impairs Helping Behavior in Rats

    Science.gov (United States)

    Ben-Ami Bartal, Inbal; Shan, Haozhe; Molasky, Nora M. R.; Murray, Teresa M.; Williams, Jasper Z.; Decety, Jean; Mason, Peggy

    2016-01-01

    Despite decades of research with humans, the biological mechanisms that motivate an individual to help others remain poorly understood. In order to investigate the roots of pro-sociality in mammals, we established the helping behavior test, a paradigm in which rats are faced with a conspecific trapped in a restrainer that can only be opened from the outside. Over the course of repeated test sessions, rats exposed to a trapped cagemate learn to open the door to the restrainer, thereby helping the trapped rat to escape (Ben-Ami Bartal et al., 2011). The discovery of this natural behavior provides a unique opportunity to probe the motivation of rodent helping behavior, leading to a deeper understanding of biological influences on human pro-sociality. To determine if an affective response motivates door-opening, rats receiving midazolam, a benzodiazepine anxiolytic, were tested in the helping behavior test. Midazolam-treated rats showed less helping behavior than saline-treated rats or rats receiving no injection. Yet, midazolam-treated rats opened a restrainer containing chocolate, highlighting the socially specific effects of the anxiolytic. To determine if midazolam interferes with helping through a sympatholytic effect, the peripherally restricted beta-adrenergic receptor antagonist nadolol was administered; nadolol did not interfere with helping. The corticosterone response of rats exposed to a trapped cagemate was measured and compared to the rats’ subsequent helping behavior. Rats with the greatest corticosterone responses showed the least helping behavior and those with the smallest responses showed the most consistent helping at the shortest latency. These results are discussed in terms of their implications for the interaction between stress and pro-social behavior. Finally, we observed that door-opening appeared to be reinforcing. A novel analytical tool was designed to interrogate the pattern of door-opening for signs that a rat’s behavior on one

  18. Finding prefrontal cortex in the rat.

    Science.gov (United States)

    Leonard, Christiana M

    2016-08-15

    The prefrontal cortex of the rat. I. Cortical projection of the mediodorsal nucleus. II. Efferent connections The cortical projection field of the mediodorsal nucleus of the thalamus (MD) was identified in the rat using the Fink-Heimer silver technique for tracing degenerating fibers. Small stereotaxic lesions confined to MD were followed by terminal degeneration in the dorsal bank of the rhinal sulcus (sulcal cortex) and the medial wall of the hemisphere anterior and dorsal to the genu of the corpus callosum (medial cortex). No degenerating fibers were traced to the convexity of the hemisphere. The cortical formation receiving a projection from MD is of a relatively undifferentiated type which had been previously classified as juxtallocortex. A study of the efferent fiber connections of the rat׳s MD-projection cortex demonstrated some similarities to those of monkey prefrontal cortex. A substantial projection to the pretectal area and deep layers of the superior colliculus originates in medial cortex, a connection previously reported for caudal prefrontal (area 8) cortex in the monkey. Sulcal cortex projects to basal olfactory structures and lateral hypothalamus, as does orbital frontal cortex in the monkey. The rat׳s MD-projection cortex differs from that in the monkey in that it lacks a granular layer and appears to have no prominent direct associations with temporal and juxtahippocampal areas. Furthermore, retrograde degeneration does not appear in the rat thalamus after damage to MD-projection areas, suggesting that the striatum or thalamus receives a proportionally larger share of the MD-projection in this animal than it does in the monkey. Comparative behavioral investigations are in progress to investigate functional differences between granular prefrontal cortex in the primate and the relatively primitive MD-projection cortex in the rat. © 1969. This article is part of a Special Issue entitled SI:50th Anniversary Issue. Copyright © 2016 Elsevier B

  19. Neuropharmacological effects of deltamethrin in rats

    OpenAIRE

    Manna, S.; Bhattacharyya, D.; Mandal, T. K.; Dey, S.

    2006-01-01

    This study examined the effect of deltamethrin on some of the neuropharmacological paradigms in a rat brain such as the motor co-ordination test using a rotarod, the pentobarbitone-induced sleeping time and pentylenetetrazole (PTZ)-induced convulsion as well as the gamma aminobutyric acid (GABA) level. Albino Wistar rats were used as the experimental animals. Different neuropharmacological paradigms such as the motor co-ordination by the rotarod, pentobarbitone-induced sleeping time and the P...

  20. Age dependence of rat liver function measurements

    DEFF Research Database (Denmark)

    Fischer-Nielsen, A; Poulsen, H E; Hansen, B A

    1989-01-01

    Changes in the galactose elimination capacity, the capacity of urea-N synthesis and antipyrine clearance were studied in male Wistar rats at the age of 8, 20 and 44 weeks. Further, liver tissue concentrations of microsomal cytochrome P-450, microsomal protein and glutathione were measured. All...... weight in the age range studied. Glutathione showed an increase of 35% from 8 to 44 weeks of age expressed per g liver. Careful age matching of control animals is important for experimental rat studies....

  1. Epidermal growth factor in the rat prostate

    DEFF Research Database (Denmark)

    Tørring, Niels; Jørgensen, P E; Poulsen, Steen Seier

    1998-01-01

    Epidermal growth factor (EGF) induces proliferation in prostate epithelial and stromal cells in primary culture. This investigation was set up to characterize the time and spatial expression of EGF in the rat prostate.......Epidermal growth factor (EGF) induces proliferation in prostate epithelial and stromal cells in primary culture. This investigation was set up to characterize the time and spatial expression of EGF in the rat prostate....

  2. Oxidative stress in normal and diabetic rats.

    Science.gov (United States)

    Torres, M D; Canal, J R; Pérez, C

    1999-01-01

    Parameters related to oxidative stress were studied in a group of 10 Wistar diabetic rats and 10 control rats. The levels of total erythrocyte catalase activity in the diabetic animals were significantly (pE far greater (pvitaminA/TG, vitaminA/PUFA, vitaminA/C 18:2) were higher in the control group. Our work corroborates the findings that fatty acid metabolism presents alterations in the diabetes syndrome and that the antioxidant status is affected.

  3. From engineering to editing the rat genome

    OpenAIRE

    Meek, Stephen; Mashimo, Tomoji; Burdon, Tom

    2017-01-01

    Since its domestication over 100 years ago, the laboratory rat has been the preferred experimental animal in many areas of biomedical research (Lindsey and Baker The laboratory rat. Academic, New York, pp?1?52, 2006). Its physiology, size, genetics, reproductive cycle, cognitive and behavioural characteristics have made it a particularly useful animal model for studying many human disorders and diseases. Indeed, through selective breeding programmes numerous strains have been derived that are...

  4. Hypophysectomyinduced regression of female rat lacrimal glands. Partial restoration/maintenance by dihydrotestosterone and prolactin

    DEFF Research Database (Denmark)

    Bjerrum, Kirsten Birgitte; Azzarolo, A.M.

    1995-01-01

    Ophthalmology, hypophysectomi, rats regression, lacrimal galnds, restoration, dihydrotestosterone, prolactin......Ophthalmology, hypophysectomi, rats regression, lacrimal galnds, restoration, dihydrotestosterone, prolactin...

  5. Genetically determined differences in the resistance to myocardial infarction in Wistar and August rats.

    Science.gov (United States)

    Belkina, L M; Saltykova, V A; Pshennikova, M G

    2001-06-01

    In intact August rats, the cardiac contractile function at rest was by 76% higher than in Wistar rats, while their hearts, both intact and after acute myocardial infarction, were more resistant to isometric load than the hearts of Wistar rats. Postinfarction mortality in August rats was 18% vs. 70% in Wistar rats. Adrenoreactivity of the myocardium in August rats was decreased compared to that in Wistar rats. These peculiarities can determine high resistance of August rats to myocardial infarction.

  6. Factors influencing zinc bioavailability in rats

    International Nuclear Information System (INIS)

    Mahalko, J.R.; Johnson, P.E.; Swan, P.B.

    1986-01-01

    The amount of Zn fed, its source, and the Zn status of experimental animals may affect Zn bioavailability. To test this, rats were fed doses of Zn from ZnCl 2 or from various foods labeled extrinsically. Three weeks before and after the test meal, rats were fed an AIN diet modified in Zn content. Absorption was calculated by monitoring whole body retention and extrapolating to zero time. In rats fed 12 ppm Zn and test doses of 6 to 275 μg, absorption decreased from 80 to 50%, and the amount absorbed increased quadratically (r 2 = 0.998), but turnover was unaffected. Rats fed 38 or 77 ppm Zn absorbed less of test doses of 290, 613, or 1700 μg Zn than did those fed 12 ppm, and their Zn turnover rate was higher. In two 2 x 7 factorial experiments, rats fed 12 or 38 ppm Zn were given 16 or 98 μg Zn from 7 Zn sources. Bioavailability from some foods was higher than from ZnCl 2 except in rats eating only 12 ppm Zn and receiving the small dose. There were greater differences in bioavailability among foods when tested at the higher Zn status or dose. This may explain inconsistencies seen in comparing Zn bioavailability by traditional growth assay with that seen in 65 Zn tracer studies. The authors conclude that Zn status of the experimental animal, as well as the amount of Zn and its source, will affect Zn bioavailability

  7. Diuron-induced rat bladder epithelial cytotoxicity.

    Science.gov (United States)

    Da Rocha, Mitscheli S; Arnold, Lora L; Pennington, Karen L; Muirhead, David; Dodmane, Puttappa R; Anwar, Muhammad M; Battalora, Michael; De Camargo, João Lauro V; Cohen, Samuel M

    2012-12-01

    Diuron, a substituted urea herbicide, is carcinogenic to the rat urinary bladder at high dietary levels (2500 ppm). To further elucidate the mode of action, this study aimed to determine the time course and sequence of bladder cytotoxic and proliferative changes induced by diuron treatment of male Wistar rats. Rats were randomized into two groups (control and 2500 ppm diuron) and treated for 28 days. Ten rats from each group were terminated on each of study days 1, 3, 7, or 28. Scanning electron micro scopy (SEM) showed urothelial cell swelling beginning on day 1, and by day 28, showed extensive necrosis, exfoliation and piling up of cells suggestive of hyperplasia. No difference in the bromo deoxyuridine labeling index was detected. In a second experiment, rats were randomized into control and diuron-treated groups and treated for 7 days or 8 weeks. After 7 days, transmission electron microscopy showed cell degenerative changes and distention of the cytoplasm, organelles, and nuclei characteristic of cytolysis. This resulted in protrusion of the superficial cells into the lumen, corresponding to the cell swelling observed previously by SEM. After 8 weeks, bladders in the diuron-treated group showed an increased incidence of simple hyperplasia by light microscopy (6/10, p diuron exposure in rats.

  8. Hematological Characteristics of the BB Wistar Rat.

    Science.gov (United States)

    Wright, J R; Yates, A J; Shah, N T; Neff, J C; Covey, D W; Thibert, P

    1983-01-01

    Complete blood counts, differential white blood cell and platelet counts were performed on male and female BB Wistar diabetic rats (BBWd), their nondiabetic siblings (BBWnd) and outbred Wistar rats of the line from which the BB Wistar rats were derived. Most of the observed changes were strain-related (those present in both BBWd and BBWnd but not in control rats) rather than diabetes-related (those in BBWd but neither BBWnd nor control rats) and therefore probably due to the inbreeding process. The BBW strain had significantly lower numbers of white cells and platelets, as well as markedly changed differential white cell counts. Differential counts showed a pattern of lymphopenia, neutrophilia, monocytosis and eosinophilia. It is possible that these white blood cell changes contribute to the increased susceptibility to infection reported for the BBW strain. No significant difference in serum immunoglobulin concentrations was found in any of these three groups of rats. There- fore, hypogammaglobutinemia cannot account for the increased susceptibility to infections, but it is not possible to rule out an abnormality in the distribution of immunoglobulin fractions as an etiological factor.

  9. Radiation nephropathy in young and adult rats

    International Nuclear Information System (INIS)

    Jongejan, H.T.; van der Kogel, A.J.; Provoost, A.P.; Molenaar, J.C.

    1987-01-01

    The effects of bilateral kidney irradiation were compared in young and adult rats. During a 1 year period after a single dose of 0, 7.5, 10, 12.5, or 15 Gy on both kidneys, renal function (glomerular filtration rate and effective renal plasma flow), urine composition, and systolic blood pressure were measured periodically. The first changes after irradiation were observed in the glomerular filtration rate and urine osmolality. One month after 10, 12.5, and 15 Gy, glomerular filtration rate (GFR) and urine osmolality had declined below control values in the young rats. After this initial decline, renal function increased at control rate or even more during the third and fourth month after irradiation but decreased progressively thereafter. In the adult rats, GFR and urine osmolality started to decrease 3 months after 10, 12.5, and 15 Gy. A rise in systolic blood pressure and proteinuria started 2-3 months after 12.5 and 15 Gy in both age groups. Early changes in the glomerular filtration rate with a drop in urine osmolality in young rats, occurring during a period of rapid renal development indicated an irradiation-induced inhibition of glomerular and tubular development. Although renal function deteriorated at a later time in adult rats, dose-response relationships obtained in young and adult rats did not show significant differences

  10. Thermoregulation in hypergravity-acclimated rats

    Science.gov (United States)

    Monson, Conrad B.; Patterson, Susan L.; Horowitz, John M.; Oyama, Jiro

    1989-01-01

    The effect of acclimation to hypergravity on thermoregulatory responses of rats was determined by comparing data on core temperature, T(c), tail temperature, and O2 consumption in rats raised at 1 G (C) and at 2.1 G. It was found that, when C rats were exposed to an ambient temperature of 9 C concurrently with exposure to 2.1 G, the T(c) fell by about 6 C, while in rats acclimated to 2.1 G, the T(c) fell only by 1 C. Results of O2 consumption measurements showed that C rats exposed simultaneously to cold and hypergravity were not activating their thermogenic mechanism sufficiently to prevent a fall in T(c). In other experiments, rats acclimated to either 1 or 2.1 G were found to lack the ability to maintain their T(c) when exposed to a 5.8-G field or when cold-stressed at 1 G for extended times.

  11. Elimination of mercury from amalgam in rats

    Energy Technology Data Exchange (ETDEWEB)

    Galic, N. [Dept. of Dental Pathology, School of Dentistry, Zagreb (Croatia); Prpic-Mehicic, G.; Prester, Lj.; Blanusa, M. [Inst. for Medical Research and Occupational Health, Zagreb (Croatia); Krnic, Z.; Erceg, D. [Pliva Pharmaceutical Co., Biomedicine Research Inst. ' ' Pliva' ' , Zagreb (Croatia)

    2001-07-01

    The aim of this study was to measure the urinary mercury excretion in rats exposed to amalgam over a two months period. Animals were either exposed to mercury from 4 dental amalgams or fed the diet containing powdered amalgams. The results showed significantly higher mercury amount in urine of both exposed groups than in control. Even two months after the amalgam had been placed in rats teeth, the amount of mercury in the urine remained 4-5 times higher than in control, and 4 times higher than in rats exposed to diet containing powdered amalgam. The elevated urinary Hg amount was accompanied by an increased level of total protein in urine. In the same exposure period the excretion of total protein in urine of rats with amalgam fillings was 2 times higher than in control and 1.5 times higher than in rats exposed to amalgam through diet. Concentrations of mercury in the sera of all groups were below the detection limit of the method. The results show that amount of mercury and protein in the urine of rats were related to the mercury release from dental amalgam. (orig.)

  12. Radio protective effects of selenium on rats

    International Nuclear Information System (INIS)

    Bakir, A.; Alya, G

    2005-11-01

    Potential radio-protective effects of different selenium supplement concentrations of 4, 8, 15 and 30 ppm were evaluated in rats. Four groups of rats were administered different concentrations of selenium in drinking water for 30 days before irradiation starting from the ablactation which considered as day 0. The results showed that the sodium selenite of 4 ppm and 8 ppm enhance the 30-day survival of irradiated rats at 7 Gy ( sup 6 sup 0 Co source, whole body irradiation dose rate of 1 Gy x min sup - sup 1) compared to the control group. The mean cumulated probability of survival of rats was 69%+-6 (mean+-S.E.) and 77%+-6 in 4 and 8 ppm groups, respectively, versus 42%+-9 for control group (P<0.001). It was also indicated that sodium selenite with concentrations of 15 and 30 ppm had no significant reduction in mortality. The mean cumulated probability of survival of rats was 50%+-12 (P=0.39) and 49%+-14 (P=0.04), respectively. The toxic effects of selenium were observed at 15 ppm and 30 ppm, survivals after 30 days of selenium intake were 76% and 46%, respectively. It was concluded that 4 and 8 ppm sodium selenite have a radio-protective effect. 15 and 30 ppm sodium selenite had no radio-protective effects in rats, this may be due to a synergism of toxicity and radiation effects. (author)

  13. Reproductive toxicity of Samanea tubulosa on rats

    Directory of Open Access Journals (Sweden)

    Maria Rafaella Luz de Araújo

    2015-12-01

    Full Text Available Samanea tubulosa is a plant used for medicinal and feeding purposes. However, ingestion of S. tubulosa pods has been associated with bovine abortion. Thus, the aim of this work was to investigate the effects of diet containing 5% of S. tubulosa pod meal on male and female Wistar rats. Diet was administered to male rats (n = 10 for 60 days before mating. Female rats (n = 10 received the treatment for 30 days, during cohabitation and from gestational day (GD 0 to GD20. Treated animals were mated with untreated rats. In male rats, plant consumption caused decreased food consumption and 20% fertility index reduction. Litters from treated males presented lower body weight and crown–rump length. Female rats treated with the plant increased water and food intake and body weight. Decreases in fertility, fecundity and gestation indices and increase of placenta weight and mean number of corpora lutea were found. Thus, owing to the possible general and reproductive toxic effects, long-term consumption of S. tubulosa is not recommended for phytotherapic or food purposes.

  14. Comparative phenotypic and cytochemical characteristics of lymphocytes of Wistar rats and rats with genetic predisposition to catalepsy after retabolil administration.

    Science.gov (United States)

    Panteleeva, N G; Shurlygina, A V; Trufakin, V A

    2013-11-01

    We studied the possibility of using anabolic steroid retabolil injections for complex correction of behavioral and immune parameters in rats with genetic predisposition to catalepsy. Subpopulation composition of lymphoid organ and blood cells was compared in rats with genetic predisposition to catalepsy and Wistar rats after retabolil administration. In rats predisposed to catalepsy, retabolil reduced the total content of thymus cells and increased absolute count of CD8 (+) thymocytes. In Wistar rats, retabolil increased the total cell count and the content of CD4 (+) thymocytes, but reduced the number of CD8 (+) cells. Therefore, changes in the subpopulation composition of thymus cells after retabolil administration were opposite in rats with genetic predisposition to catalepsy and Wistar rats. Retabolil injections reduced the severity of catalepsy response in rats with genetic predisposition. However, the time of freezing in Wistar rats significantly increased under these conditions.

  15. [Preventive effects of pueraria on presbycusis in rats].

    Science.gov (United States)

    Chen, Wangyan; Yao, Qi; Liu, Weihong; Zhang, Bibo; Wang, Ying; Liu, Bo

    2009-08-01

    To investigate the preventive effects of Pueraria on presbycusis in rats. Thirty-two 24-26 month old Wistar rats were randomly divided into four groups, and were treated with different dosages of Pueraria (1, 2, 4, 0 g x kg(-1) x d(-1)) separately for 4 weeks. Auditory brainstem response (ABR) was used to detect the change of hearing threshold of rats. Hemorheological items of rats were checked in each group. Compared with control group, the hearing threshold and hemorheological items of rats was significantly improved after treated with Pueraria (Ppresbycusis of rats.

  16. Genetic influence on brain catecholamines: high brain norepinephrine in salt-sensitive rats

    Energy Technology Data Exchange (ETDEWEB)

    Iwai, J; Friedman, R; Tassinari, L

    1980-01-01

    Rats genetically sensitive to salt-induced hypertension evinced higher levels of plasma norepinephrine and epinephrine than rats genetically resistant to hypertension. The hypertension-sensitive rats showed higher hypothalamic norepinephrine and lower epinephrine than resistant rats. In response to a high salt diet, brain stem norepinephrine increased in sensitive rats while resistant rats exhibited a decrease on the same diet.

  17. Genetic influence on brain catecholamines: high brain noradrenaline in salt-sensitive rats

    Energy Technology Data Exchange (ETDEWEB)

    Iwai, J.; Friedman, R.; Tassinari, L.

    1980-01-01

    Rats genetically sensitive to salt-induced hypertension showed higher levels of plasma noradrenaline and adrenaline than rats genetically resistant to hypertension. The hypertension-sensitive rats had higher hypothalamic noradrenaline and lower adrenaline than resistant rats. In response to a high salt diet brain-stem noradrenaline increased in sensitive rats and resistant rats exhibited a decrease on the same diet.

  18. Increased radiosensitivity of cerebral capillaries in neonatal Gunn rats as compared to Sprague-Dawley rats

    International Nuclear Information System (INIS)

    Landolt, R.; Arn, D.

    1979-01-01

    The extent of petechial haemorrhages of the cerebral cortex examined between 14 hours and 4 days after X-irradiation to the head was compared in Sprague-Dawley and homozygous Gunn rats with congenital hyperbilirubinaemia. Animals 1 to 2 days old received single doses of either 250, 500 or 750 rad. By means of a special scoring scale the degree of the damage to the micro vasculature was semi-quantitatively estimated. In both strains a significant difference in effect was obtained between 250 and 500 rad, but not between 500 and 750 rad. The shape of the dose-effect curve in Gunn rats was similar to that of Sprague-Dawley rats, but displaced upwards. In Gunn rats the effect of 250 rad was greater that that of 750 rad in Sprague-Dawley rats. Possible radiosensitizing mechanisms are discussed with reference to the literature and these results. (author)

  19. Population Structure of Rat-Derived Pneumocystis carinii in Danish Wild Rats

    DEFF Research Database (Denmark)

    Palmer, Robert J.; Settnes, Osvald P.; Lodal, Jens

    2000-01-01

    . carinii DNA was detected in 47 of 51 wild rats and in 10 of 12 nonimmunosuppressed laboratory rats. Evidence for three novel formae speciales of rat-derived P. carinii was found, and these were provisionally named Pneumocystis carinii f. sp. rattus-secundi, Pneumocystis carinii f. sp. rattus...... samples. We report a lack of variation in the ITS1 and ITS2 regions that is consistent with an evolutionary bottleneck in the P. carinii f. sp. carinii population. This study shows that human- and rat-derived P. carinii organisms are very different, not population. This study shows that human- and rat-derived...... organisms are very different, not only in genetic composition but also in population structure and natural history....

  20. Social structure predicts genital morphology in African mole-rats.

    Directory of Open Access Journals (Sweden)

    Marianne L Seney

    2009-10-01

    Full Text Available African mole-rats (Bathyergidae, Rodentia exhibit a wide range of social structures, from solitary to eusocial. We previously found a lack of sex differences in the external genitalia and morphology of the perineal muscles associated with the phallus in the eusocial naked mole-rat. This was quite surprising, as the external genitalia and perineal muscles are sexually dimorphic in all other mammals examined. We hypothesized that the lack of sex differences in naked mole-rats might be related to their unusual social structure.We compared the genitalia and perineal muscles in three African mole-rat species: the naked mole-rat, the solitary silvery mole-rat, and the Damaraland mole-rat, a species considered to be eusocial, but with less reproductive skew than naked mole-rats. Our findings support a relationship between social structure, mating system, and sexual differentiation. Naked mole-rats lack sex differences in genitalia and perineal morphology, silvery mole-rats exhibit sex differences, and Damaraland mole-rats are intermediate.The lack of sex differences in naked mole-rats is not an attribute of all African mole-rats, but appears to have evolved in relation to their unusual social structure and reproductive biology.

  1. Social structure predicts genital morphology in African mole-rats.

    Science.gov (United States)

    Seney, Marianne L; Kelly, Diane A; Goldman, Bruce D; Sumbera, Radim; Forger, Nancy G

    2009-10-15

    African mole-rats (Bathyergidae, Rodentia) exhibit a wide range of social structures, from solitary to eusocial. We previously found a lack of sex differences in the external genitalia and morphology of the perineal muscles associated with the phallus in the eusocial naked mole-rat. This was quite surprising, as the external genitalia and perineal muscles are sexually dimorphic in all other mammals examined. We hypothesized that the lack of sex differences in naked mole-rats might be related to their unusual social structure. We compared the genitalia and perineal muscles in three African mole-rat species: the naked mole-rat, the solitary silvery mole-rat, and the Damaraland mole-rat, a species considered to be eusocial, but with less reproductive skew than naked mole-rats. Our findings support a relationship between social structure, mating system, and sexual differentiation. Naked mole-rats lack sex differences in genitalia and perineal morphology, silvery mole-rats exhibit sex differences, and Damaraland mole-rats are intermediate. The lack of sex differences in naked mole-rats is not an attribute of all African mole-rats, but appears to have evolved in relation to their unusual social structure and reproductive biology.

  2. Policosanol prevents bone loss in ovariectomized rats.

    Science.gov (United States)

    Noa, M; Más, R; Mendoza, S; Gámez, R; Mendoza, N; González, J

    2004-01-01

    Osteoporosis is characterized by reduced bone mass, abnormal bone architecture and increased fracture risk. Ovariectomy impairs bone mass and metabolism in rats and ovariectomized rats are considered as a suitable model of postmenopausal osteoporosis. Mevalonate is required for producing lipoids that are important in osteoclast activity and thus drugs affecting mevalonate production can prevent bone loss in rodents. Policosanol is a cholesterol-lowering drug isolated from sugar cane wax that inhibits cholesterol biosynthesis through an indirect regulation of hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase activity. The purpose of this study was to determine whether policosanol could prevent bone loss in the bones of ovariectomized rats by comparing its effects with those induced by estradiol. Sprague Dawley female rats were randomly distributed in four groups: a sham-operated group treated with Tween/H2O vehicle and three groups of ovariectomized rats treated with 17beta-estradiol (30 microg/kg/day) or policosanol (50 and 200 mg/kg/day), respectively, for 3 months. At treatment completion the rats were sacrificed, their bones removed and variables of bone resorption and formation were investigated by histomorphometry. Ovariectomy increased trabecular separation but diminished the number and thickness of trabecules. Estradiol and policosanol prevented these effects compared with ovariectomized controls. Both treatments also prevented an increase in the number of osteoclasts and their surface area induced by ovariectomy. Estradiol, but not policosanol, significantly prevented an increase of osteoblast surface area compared with ovariectomized controls. In conclusion, policosanol prevented bone loss and decreased bone resorption in ovariectomized rats, suggesting that it should be potentially useful in preventing bone loss in postmenopausal women.

  3. Thyroid hormone action on rat calvarial sutures.

    Science.gov (United States)

    Akita, S; Nakamura, T; Hirano, A; Fujii, T; Yamashita, S

    1994-01-01

    To clarify the effect of thyroid hormone on the calvarial sutures, the morphology, histology, and bone mineral density were analyzed in thyroid hormone-injected rats. A total of 80 female Wistar rats at the age of 10 days were divided into 2 groups; the triiodothyronine (T3)-treated rats (n = 40, T3 100 micrograms/kg body weight/day) were maintained under the same conditions as controls (n = 40, saline-vehicle only), and both were sacrificed at 50, 80, and 200 experimental days, respectively. T3-treated animals showed smaller values of lambda-asterion and pterion-bregma distances at the various periods of examination, resulting in smaller sizes in right-left direction of the skull. The sagittal suture distance in the skull specimens observed by Goldner's staining (fibrous tissue content) appeared smaller and the osseous margin widths greatly increased in the T3-treated rats. Fluorescent microscopy revealed that the tetracycline-calcein double labelings were not interrupted from the periosteal to the endosteal areas in any specimens indicating the scantiness of osteoclastic activity in the suture areas. Mineral apposition rates at the osseous edges of the suture were significantly increased in the T3-treated rats (p < 0.01 at the age of 90 days). The distance between the second labels and the distance between the first labels were significantly larger in the T3-treated rats. Bone mineral density (BMD) measurement showed that the T3 administration decreased only the calvarial BMD at the age of 210 days (p < 0.01), but did not decrease lumbar or femur BMD. This experiment demonstrated clear evidence of excess thyroid hormone action on the early narrowing of the sagittal suture in infantile hyperthyroid rats, probably due to the enhanced osteogenic activity caused by the hormone.

  4. Absorption of plutonium in the iron-deficient rat

    International Nuclear Information System (INIS)

    Ragan, H.A.

    1977-01-01

    Iron deficiency did not enhance absorption of plutonium following intragastric gavage of rats. Absorption of plutonium citrate in both control and iron-deficient rats was about 0.03% of the administered dose

  5. Comparative efficacy of Berenil and Samorin in albino rats ...

    African Journals Online (AJOL)

    Berenil-therapeutic) and isometamidium chloride (Samorin-prophylactic) was compared in albino rats experimentally infected with current field isolate of Trypanosoma brucei brucei (Federe strain). The study consisted of forty albino rats, divided ...

  6. In vitro biotransformation of flavonoids by rat liver microsomes

    DEFF Research Database (Denmark)

    Nielsen, S. E.; Breinholt, V.; Justesen, U.

    1998-01-01

    1. Sixteen naturally occurring flavonoids were investigated as substrates for cytochrome P450 in uninduced and Aroclor 1254-induced rat liver microsomes. Naringenin, hesperetin, chrysin, apigenin, tangeretin, kaempferol, galangin and tamarixetin were all metabolized extensively by induced rat liver...

  7. Mechanisms underlying epithelium-dependent relaxation in rat bronchioles

    DEFF Research Database (Denmark)

    Kroigaard, Christel; Dalsgaard, Thomas; Simonsen, Ulf

    2010-01-01

    This study investigated the mechanisms underlying epithelium-derived hyperpolarizing factor (EpDHF)-type relaxation in rat bronchioles. Immunohistochemistry was performed, and rat bronchioles and pulmonary arteries were mounted in microvascular myographs for functional studies. An opener of small...

  8. Water metabolism and modification of tritium excretion in the rat

    International Nuclear Information System (INIS)

    Ichimasa, Y.; Akita, Y.

    1982-01-01

    1. The intake and excretion of tritium were studied in rats exposed to tritiated water vapor. The metabolism of tritium was also investigated in rats given single administrations of tritiated water and in rats given daily administrations (per os or i.p.). The results were essentially in accord with those reported previously. 2. Amounts of drinking water consumed and urine excreted by rats drinking water with 0.15% saccharin were 1.5 to 2 times higher than in rats drinking tap water. The tritium activity in various tissues of rats drinking water with 0.15% saccharin decreased to about half of that of rats drinking tap water. A similar tendency was observed also in rats drinking beer. The diuretic agent sodium acetazolamide also enhanced the urinary excretion of tritium. (author)

  9. [Pinealectomy and early castration in the female Wistar rat].

    Science.gov (United States)

    Slama-Scemama, A

    1976-05-17

    Pinealectomy does not significantly modify the level of pituitary and plasma gonadotropins in intact and in castrated female Rats from brith to 75 days of age. Only the weight of the thyroid gland is higher in pinealectomized rats.

  10. Patterns of blood pressure variability in normotensive and hypertensive rats

    DEFF Research Database (Denmark)

    Holstein-Rathlou, N H; He, J; Wagner, A J

    1995-01-01

    We sought patterns in mean arterial pressure of normotensive rats and alterations in chronic hypertension. Pressure was recorded for 4-6 days by telemetry from conscious, unrestrained rats and sampled digitally at 3 Hz, using normotensive Sprague-Dawley rats, spontaneously hypertensive rats (SHR)...... the day; less pronounced in 2K,1C; and not detectable in SHR. There are regular patterns of blood pressure fluctuations and specific modifications to the patterns by different forms of hypertension.......We sought patterns in mean arterial pressure of normotensive rats and alterations in chronic hypertension. Pressure was recorded for 4-6 days by telemetry from conscious, unrestrained rats and sampled digitally at 3 Hz, using normotensive Sprague-Dawley rats, spontaneously hypertensive rats (SHR...

  11. The effect of Mansoniaaltisma on haematological parameters of rat ...

    African Journals Online (AJOL)

    The test rats were treated orally by intubations with 0.5, 1.0 and 2.0 g of Mansonia extract per kilogram body weight of rat respectively (the doses were administered in 2.5 ml. of deionized water). Control rats were administered the same volume of deionized water (2.5 ml.). Rats administered the highest dose of the extract ...

  12. WTC rat has unique characteristics such as resistant to streptozotocin

    OpenAIRE

    Nagaki, Yoshiaki; Ito, Koichi; Kuwahara, Masayoshi

    2016-01-01

    Because we found that WTC rats might be resistant to streptozotocin (STZ), we have elucidated the mechanisms of resistant to the diabetogenic effects of STZ in the WTC rats. Dose response to STZ was evaluated with glucose levels. No significant changes in glucose level to STZ administration were observed in WTC rats. Insulin secretion by suppling glucose was preserved in WTC rats even after STZ administration. Although there was no significant difference in gene expression of both GLUT2 and K...

  13. Biological effects of 137Cs, incorporated into organism of rats

    International Nuclear Information System (INIS)

    Monakhov, A.S.; Strekalov, S.A.; Sokolov, A.V.; Aver'yanova, T.K.

    1987-01-01

    Results of investigating mutagenous and hemotoxic effects of 137 Cs on blood lymphocytes of rats are presented. 137 Cs was orally administrated into organism of rats as 270 kBq/g chloride solution. 137 Cs mutagenous effect was studied on metaphase plates of rat blood lymphocytes in course of rats lifetime experiment. It is stated that 137 Cs inducing severe disturbances of genetic material in a great quantity of blood lymphocytes, causes their total killing

  14. Tumorigenicity of sodium ascorbate in male rats.

    Science.gov (United States)

    Cohen, S M; Anderson, T A; de Oliveira, L M; Arnold, L L

    1998-06-15

    Sodium ascorbate, like other sodium salts such as saccharin, glutamate, and bicarbonate, produces urinary alterations when fed at high doses to rats, which results in mild superficial urothelial cytotoxicity and regeneration but not tumors in a standard 2-year bioassay. Sodium saccharin was shown to produce a low incidence of bladder tumors in rats if administered in a two-generation bioassay. In the present study, we evaluated sodium ascorbate in a two-generation bioassay that involved feeding to the male and female parental F344 rats for 4 weeks before mating, feeding the dams during gestation and lactation, and then feeding the weaned (at 28 days of age) male F1 generation rats for the remainder of their lifetime (up to 128 weeks of the experiment). Dietary levels of 1.0, 5.0, and 7.0% sodium ascorbate were tested. At 5.0 and 7.0% sodium ascorbate, there was an increase in urinary bladder urothelial papillary and nodular hyperplasia and the induction of a few papillomas and carcinomas. There was a dose-responsive increase in renal pelvic calcification and hyperplasia and inhibition of the aging nephropathy of rats even at the level of 1% sodium ascorbate. Because the short-term urothelial effects of sodium ascorbate in rats are inhibited by treatments producing urinary acidification to pH sodium ascorbate to evaluate the long-term effects. The combination of 7.0% sodium ascorbate plus 2.78% NH4Cl in the diet was toxic, and the group was terminated early during the course of the experiment. The group fed 5.0% sodium ascorbate plus 2.04% NH4Cl showed complete inhibition of the urothelial effects of sodium ascorbate and significant inhibition of its renal effects. We also demonstrated the presence of a calcium phosphate-containing urinary precipitate in rats fed sodium ascorbate at all doses, in a dose-responsive manner. The formation of the precipitate was inhibited by coadministration with NH4Cl. The proliferative effects of sodium ascorbate on the male rat

  15. Nigella Sativa reverses osteoporosis in ovariectomized rats.

    Science.gov (United States)

    Seif, Ansam Aly

    2014-01-14

    Osteoporosis poses a significant public health issue. It is a skeletal disorder characterized by compromised bone strength that predisposes to increased risk of fracture. There is a direct relationship between the lack of estrogen after menopause and the development of osteoporosis. About 33% of women over 50 will experience bone fractures as a result of osteoporosis. Nigella Sativa (NS) has been shown to have beneficial effects on bone and joint diseases. The present study was conducted to elucidate the protective effect of Nigella Sativa on osteoporosis produced by ovariectomy in rats. Female Wistar rats aged 12-14 months were divided into three groups: sham-operated control (SHAM), ovariectomized (OVX), and ovariectomized supplemented with nigella sativa (OVX-NS) orally for 12 weeks; 4 weeks before ovariectomy and 8 weeks after. After 12 weeks, plasma levels of calcium (Ca(+2)), phosphorous (Pi), alkaline phosphatase (ALP), amino terminal collagen type 1 telopeptide, malondialdehyde (MDA), nitrates, nitric oxide surrogate, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were measured. Histological examination of the liver and the tibia was conducted. Histomorphometric analysis of the tibia was also performed. OVX rats showed significant decrease in plasma Ca(+2), accompanied by a significant increase in plasma ALP, amino terminal collagen type 1 telopeptide, MDA, nitrates, TNF-α and IL-6. These changes were reversed by NS supplementation in OVX-NS group to be near SHAM levels. Histological examination of the tibias revealed discontinuous eroded bone trabeculae with widened bone marrow spaces in OVX rats accompanied by a significant decrease in both cortical and trabecular bone thickness compared to Sham rats. These parameters were markedly reversed in OVX-NS rats. Histological examination of the liver showed mononuclear cellular infiltration and congestion of blood vessels at the portal area in OVX rats which were not found in OVX-NS rats. Nigella

  16. From engineering to editing the rat genome.

    Science.gov (United States)

    Meek, Stephen; Mashimo, Tomoji; Burdon, Tom

    2017-08-01

    Since its domestication over 100 years ago, the laboratory rat has been the preferred experimental animal in many areas of biomedical research (Lindsey and Baker The laboratory rat. Academic, New York, pp 1-52, 2006). Its physiology, size, genetics, reproductive cycle, cognitive and behavioural characteristics have made it a particularly useful animal model for studying many human disorders and diseases. Indeed, through selective breeding programmes numerous strains have been derived that are now the mainstay of research on hypertension, obesity and neurobiology (Okamoto and Aoki Jpn Circ J 27:282-293, 1963; Zucker and Zucker J Hered 52(6):275-278, 1961). Despite this wealth of genetic and phenotypic diversity, the ability to manipulate and interrogate the genetic basis of existing phenotypes in rat strains and the methodology to generate new rat models has lagged significantly behind the advances made with its close cousin, the laboratory mouse. However, recent technical developments in stem cell biology and genetic engineering have again brought the rat to the forefront of biomedical studies and enabled researchers to exploit the increasingly accessible wealth of genome sequence information. In this review, we will describe how a breakthrough in understanding the molecular basis of self-renewal of the pluripotent founder cells of the mammalian embryo, embryonic stem (ES) cells, enabled the derivation of rat ES cells and their application in transgenesis. We will also describe the remarkable progress that has been made in the development of gene editing enzymes that enable the generation of transgenic rats directly through targeted genetic modifications in the genomes of zygotes. The simplicity, efficiency and cost-effectiveness of the CRISPR/Cas gene editing system, in particular, mean that the ability to engineer the rat genome is no longer a limiting factor. The selection of suitable targets and gene modifications will now become a priority: a challenge where

  17. Working Memory Systems in the Rat.

    Science.gov (United States)

    Bratch, Alexander; Kann, Spencer; Cain, Joshua A; Wu, Jie-En; Rivera-Reyes, Nilda; Dalecki, Stefan; Arman, Diana; Dunn, Austin; Cooper, Shiloh; Corbin, Hannah E; Doyle, Amanda R; Pizzo, Matthew J; Smith, Alexandra E; Crystal, Jonathon D

    2016-02-08

    A fundamental feature of memory in humans is the ability to simultaneously work with multiple types of information using independent memory systems. Working memory is conceptualized as two independent memory systems under executive control [1, 2]. Although there is a long history of using the term "working memory" to describe short-term memory in animals, it is not known whether multiple, independent memory systems exist in nonhumans. Here, we used two established short-term memory approaches to test the hypothesis that spatial and olfactory memory operate as independent working memory resources in the rat. In the olfactory memory task, rats chose a novel odor from a gradually incrementing set of old odors [3]. In the spatial memory task, rats searched for a depleting food source at multiple locations [4]. We presented rats with information to hold in memory in one domain (e.g., olfactory) while adding a memory load in the other domain (e.g., spatial). Control conditions equated the retention interval delay without adding a second memory load. In a further experiment, we used proactive interference [5-7] in the spatial domain to compromise spatial memory and evaluated the impact of adding an olfactory memory load. Olfactory and spatial memory are resistant to interference from the addition of a memory load in the other domain. Our data suggest that olfactory and spatial memory draw on independent working memory systems in the rat. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Cardiopulmonary Changes with Moderate Decompression in Rats

    Science.gov (United States)

    Robinson, R.; Little, T.; Doursout, M.-F.; Butler, B. D.; Chelly, J. E.

    1996-01-01

    Sprague-Dawley rats were compressed to 616 kPa for 120 min then decompressed at 38 kPa/min to assess the cardiovascular and pulmonary responses to moderate decompression stress. In one series of experiments the rats were chronically instrumented with Doppler ultrasonic probes for simultaneous measurement of blood pressure, cardiac output, heart rate, left and right ventricular wall thickening fraction, and venous bubble detection. Data were collected at base-line, throughout the compression/decompression protocol, and for 120 min post decompression. In a second series of experiments the pulmonary responses to the decompression protocol were evaluated in non-instrumented rats. Analyses included blood gases, pleural and bronchoalveolar lavage (BAL) protein and hemoglobin concentration, pulmonary edema, BAL and lung tissue phospholipids, lung compliance, and cell counts. Venous bubbles were directly observed in 90% of the rats where immediate post-decompression autopsy was performed and in 37% using implanted Doppler monitors. Cardiac output, stroke volume, and right ventricular wall thickening fractions were significantly decreased post decompression, whereas systemic vascular resistance was increased suggesting a decrease in venous return. BAL Hb and total protein levels were increased 0 and 60 min post decompression, pleural and plasma levels were unchanged. BAL white blood cells and neutrophil percentages were increased 0 and 60 min post decompression and pulmonary edema was detected. Venous bubbles produced with moderate decompression profiles give detectable cardiovascular and pulmonary responses in the rat.

  19. Opiates and cerebral functional activity in rats

    Energy Technology Data Exchange (ETDEWEB)

    Trusk, T.C.

    1986-01-01

    Cerebral activity was measured using the free-fatty acid (1-/sup 14/C) octanoate as a fast functional tracer in conscious, unrestrained rats 5 minutes after intravenous injection of heroin, cocaine or saline vehicle. Regional changes of octanoate labeling density in the autoradiograms relative to saline-injected animals were used to determine the functional activity effects of each drug. Heroin and cocaine each produced a distinctive pattern of activity increases and suppression throughout the rat brain. Similar regional changes induced by both drugs were found in limbic brain regions implicated in drug reinforcement. Labeled octanoate autoradiography was used to measure the cerebral functional response to a tone that had previously been paired to heroin injections. Rats were trained in groups of three consisting of one heroin self-administration animal, and two animals receiving yoked infusion of heroin or saline. A tone was paired with each infusion during training. Behavioral experiments in similarly trained rats demonstrated that these training conditions impart secondary reinforcing properties to the tone in animals previously self-administering heroin, while the tone remains behaviorally neutral in yoked-infusion rats. Cerebral functional activity was measured during presentation of the tone without drug infusion. Octanoate labeling density changed in fifteen brain areas in response to the tone previously paired to heroin without response contingency. Labeling density was significantly modified in sixteen regions as a result of previously pairing the tone to response-contingent heroin infusions.

  20. Hematological changes in opium addicted diabetic rats.

    Science.gov (United States)

    Asadikaram, Gholamreza; Sirati-Sabet, Majid; Asiabanha, Majid; Shahrokhi, Nader; Jafarzadeh, Abdollah; Khaksari, Mohammad

    2013-01-01

    Chronic opioid treatment in animal models has shown to alter hematological parameters. The aim of this study was to evaluate the biological effects of opium on the number of peripheral blood cells and red blood cells (RBCs) indices in diabetic rats. Peripheral blood samples were collected from diabetic, opium-addicted, diabetic opium-addicted and normal male and female rats and hematological parameters were measured. The mean number of white blood cells (WBCs) was significantly higher in diabetic opium-addict females compared to diabetic non-addict female group. In both male and female, the mean number of neutrophils was significantly higher and the mean number of lymphocytes was lower in diabetic opium-addicted rats than those observed in diabetic non-addicted group. In diabetic opium-addicted male group the mean counts of RBC significantly increased as compared with diabetic male group. However, in diabetic addicted female, the mean number of RBCs was significantly lower than diabetic non-addicted female group. In both males and females, the mean number of platelets was significantly lower in diabetic addict rats compared to diabetic non-addict group. Generally, the results indicated that opium addiction has different effects on male and female rats according to the number of WBC, RBC and RBC indices. It could also be concluded that in the opium-addicts the risk of infection is enhanced due to the weakness of immune system as a result of the imbalance effect of opium on the immune cells.

  1. Gastric secretion elicited by conditioning in rats.

    Science.gov (United States)

    Caboclo, José Liberato Ferreira; Cury, Francico de Assis; Borin, Aldenis Albanese; Caboclo, Luís Otávio Sales Ferreira; Ribeiro, Maria Fernanda Sales Caboclo; de Freitas, Pedro José; Andersson, Sven

    2009-01-01

    To investigate whether interdigestive gastric acid secretion can be controlled by a possible memory-related cortical mechanism. To evaluate gastric secretion in rats, we used a methodology that allows gastric juice collection in rats in their habitual conditions (without any restraining) by pairing sound as the conditioning stimulus (CS) and food as the unconditioning stimulus (US). The levels of gastric acid secretion under basal conditions and under sound stimulation were recorded and the circulating gastrin levels determined. When the gastric juice was collected in the course of the conditioning procedure, the results showed that under noise stimulation a significant increase in gastric acid secretion occurred after 10 days of conditioning (p<0.01). The significance was definitively demonstrated after 13 days of conditioning (p<0.001). Basal secretions of the conditioned rats reached a significant level after 16 days of conditioning. The levels of noise-stimulated gastric acid secretion were the highest so far described in physiological experiments carried out in rats and there were no significant increases in the circulating gastrin levels. The results point to the important role played by cortical structures in the control of interdigestive gastric acid secretion in rats. If this mechanism is also present in humans, it may be involved in diseases caused by inappropriate gastric acid secretion during the interprandial periods.

  2. A rat model for hepatitis E virus

    Directory of Open Access Journals (Sweden)

    Yannick Debing

    2016-10-01

    Full Text Available Hepatitis E virus (HEV is one of the prime causes of acute viral hepatitis, and chronic hepatitis E is increasingly recognized as an important problem in the transplant setting. Nevertheless, the fundamental understanding of the biology of HEV replication is limited and there are few therapeutic options. The development of such therapies is partially hindered by the lack of a robust and convenient animal model. We propose the infection of athymic nude rats with the rat HEV strain LA-B350 as such a model. A cDNA clone, pLA-B350, was constructed and the infectivity of its capped RNA transcripts was confirmed in vitro and in vivo. Furthermore, a subgenomic replicon, pLA-B350/luc, was constructed and validated for in vitro antiviral studies. Interestingly, rat HEV proved to be less sensitive to the antiviral activity of α-interferon, ribavirin and mycophenolic acid than genotype 3 HEV (a strain that infects humans. As a proof-of-concept, part of the C-terminal polymerase sequence of pLA-B350/luc was swapped with its genotype 3 HEV counterpart: the resulting chimeric replicon replicated with comparable efficiency as the wild-type construct, confirming that LA-B350 strain is amenable to humanization (replacement of certain sequences or motifs by their counterparts from human HEV strains. Finally, ribavirin effectively inhibited LA-B350 replication in athymic nude rats, confirming the suitability of the rat model for antiviral studies.

  3. Renal alterations in prediabetic rats with periodontitis

    DEFF Research Database (Denmark)

    Andersen, Carla Cruvinel Pontes; Holmstrup, Palle; Buschard, Karsten

    2008-01-01

    BACKGROUND: Periodontitis was shown to have an impact on glucose levels in prediabetic and diabetic rats. The Zucker fatty rat (ZFR) is a well-characterized model of prediabetes presenting with impaired glucose tolerance, hyperinsulinemia, dyslipidemia, and moderate hypertension. The aim of the p......BACKGROUND: Periodontitis was shown to have an impact on glucose levels in prediabetic and diabetic rats. The Zucker fatty rat (ZFR) is a well-characterized model of prediabetes presenting with impaired glucose tolerance, hyperinsulinemia, dyslipidemia, and moderate hypertension. The aim...... of the present study was to investigate whether periodontitis influences kidney changes in ZFRs. METHODS: Male adult ZFRs (N = 19) and their lean littermates (N = 18) were studied. Periodontitis was induced with ligatures in half of the ZFRs and lean rats, whereas the other half served as controls. After 4 weeks...... IValpha1, fibronectin, and nephrin. Urinary albumin excretion and creatinine clearance were also evaluated. RESULTS: In prediabetic ZFRs, periodontitis was associated with kidney hypertrophy (P = 0.03) and a tendency for increased glomerular volume (P = 0.06). In lean littermates, elevated fibronectin m...

  4. Somatostatin ontogenesis in the gastrointestinal and pancreatic tract: study in normal rats and during a induced diabetes in neonates rats

    International Nuclear Information System (INIS)

    Cunha, M.C.

    1980-01-01

    The ontogenic studies of somatostatin of pancreas, ileum and duodenum of Wistar rats and the rats with induced diabetes were done. The radioimmunologic method to dose the somatostatin was used. (L.M.J.)

  5. Origins of albino and hooded rats: implications from molecular genetic analysis across modern laboratory rat strains.

    Science.gov (United States)

    Kuramoto, Takashi; Nakanishi, Satoshi; Ochiai, Masako; Nakagama, Hitoshi; Voigt, Birger; Serikawa, Tadao

    2012-01-01

    Albino and hooded (or piebald) rats are one of the most frequently used laboratory animals for the past 150 years. Despite this fact, the origin of the albino mutation as well as the genetic basis of the hooded phenotype remained unclear. Recently, the albino mutation has been identified as the Arg299His missense mutation in the Tyrosinase gene and the hooded (H) locus has been mapped to the ∼460-kb region in which only the Kit gene exists. Here, we surveyed 172 laboratory rat strains for the albino mutation and the hooded (h) mutation that we identified by positional cloning approach to investigate possible genetic roots and relationships of albino and hooded rats. All of 117 existing laboratory albino rats shared the same albino missense mutation, indicating they had only one single ancestor. Genetic fine mapping followed by de novo sequencing of BAC inserts covering the H locus revealed that an endogenous retrovirus (ERV) element was inserted into the first intron of the Kit gene where the hooded allele maps. A solitary long terminal repeat (LTR) was found at the same position to the ERV insertion in another allele of the H locus, which causes the so called Irish (h(i)) phenotype. The ERV and the solitary LTR insertions were completely associated with the hooded and Irish coat patterns, respectively, across all colored rat strains examined. Interestingly, all 117 albino rat strains shared the ERV insertion without any exception, which strongly suggests that the albino mutation had originally occurred in hooded rats.

  6. Fetal rat pancreas transplantation in BB rats: immunohistochemical and functional evaluation.

    Science.gov (United States)

    Yderstraede, K B; Starklint, H; Steinbruchel, D; Jørgensen, T W; Gotfredsen, C F

    1993-01-01

    Spontaneously diabetic BB/Wor rats received either a syngeneic fetal pancreas transplant or adult islets. In the former, 4-8 fetal pancreases were transplanted, and in the latter, 3-5000 islets. Transplantation was performed by transferring a blood clot containing the pancreases or islets to the renal subcapsular space. Insulin therapy was undertaken postoperatively, except in one experiment with adult islets. Of the fetal pancreas transplanted BB rats, 52% became normoglycaemic, and 21% remained so throughout an observation period of 10 months. Nephrectomy caused a prompt return of diabetes. The histological appearance of the grafts transplanted to the diabetic animals closely resembled that of grafts transplanted to normal rats in a parallel series. For comparison a group of BB rats received a syngeneic transplant of isolated adult islets from WF rats or BBW rats. Following adult islet transplantation, 5 out of 6 animals became hyperglycaemic after a median of 20.5 days when no insulin was given post-transplantation. Four out of 5 animals became hyperglycaemic after a median of 23 days when supportive insulin therapy was administered after the transplantation. The results indicate that recurrent diabetes is not inevitable following syngeneic fetal pancreas transplantation to spontaneously diabetic BB rats. Recurrent diabetes was only occasionally associated with mononuclear cell infiltration. Transplanted tissue was well-preserved and vascularized; mega-islets were a constant finding.

  7. Phenotypic Characterization of LEA Rat: A New Rat Model of Nonobese Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Tadashi Okamura

    2013-01-01

    Full Text Available Animal models have provided important information for the genetics and pathophysiology of diabetes. Here we have established a novel, nonobese rat strain with spontaneous diabetes, Long-Evans Agouti (LEA rat derived from Long-Evans (LE strain. The incidence of diabetes in the males was 10% at 6 months of age and 86% at 14 months, while none of the females developed diabetes. The blood glucose level in LEA male rats was between 200 and 300 mg/dl at 120 min according to OGTT. The glucose intolerance in correspondence with the impairment of insulin secretion was observed in male rats, which was the main cause of diabetes in LEA rats. Histological examination revealed that the reduction of β-cell mass was caused by progressive fibrosis in pancreatic islets in age-dependent manner. The intracytoplasmic hyaline droplet accumulation and the disappearance of tubular epithelial cell layer associated with thickening of basement membrane were evident in renal proximal tubules. The body mass index and glycaemic response to exogenous insulin were comparable to those of control rats. The unique characteristics of LEA rat are a great advantage not only to analyze the progression of diabetes, but also to disclose the genes involved in type 2 diabetes mellitus.

  8. Effect of Yushen zhuyun decoction on rats with diminished ovarian ...

    African Journals Online (AJOL)

    Purpose: To investigate the effect of Yushen zhuyun decoction (YSZYF) on rats with diminished ovarian reserve (DOR). Methods: High-performance liquid chromatography (HPLC) was used to determine the major phytochemical constituents of YSZYF. Rats with DOR (DOR rats) were prepared by administration of ...

  9. Effect of thiabendazole on some rat hepatic xenobiotic metabolising enzymes

    NARCIS (Netherlands)

    Price, R.J.; Scott, M.P.; Walters, D.G.; Stierum, R.H.; Groten, J.P.; Meredith, C.; Lake, B.G.

    2004-01-01

    The effect of thiabendazole (TB) on some rat hepatic xenobiotic metabolising enzymes has been investigated. Male Sprague-Dawley rats were fed control diet or diets containing 102-5188 ppm TB for 28 days. As a positive control for induction of hepatic xenobiotic metabolism, rats were also fed diets

  10. Haematological and Serum Biochemical Variables in rats Treated ...

    African Journals Online (AJOL)

    The haematology and serum biochemical effects of oral administration of the ethanolic extract of the root of Moringa oleifera at 50, 100 and 150 mg/kg were investigated in 30 mated female Wistar rats. The rats were assigned into five groups of six rats each. Group A was given 50mg/kg of the extract; group B, 100mg/kg; ...

  11. Rat1p maintains RNA polymerase II CTD phosphorylation balance

    DEFF Research Database (Denmark)

    Jimeno-González, Silvia; Schmid, Manfred; Malagon, Francisco

    2014-01-01

    In S. cerevisiae, the 5'-3' exonuclease Rat1p partakes in transcription termination. Although Rat1p-mediated RNA degradation has been suggested to play a role for this activity, the exact mechanisms by which Rat1p helps release RNA polymerase II (RNAPII) from the DNA template are poorly understoo...

  12. Rat-to-human transmission of Cowpox infection

    NARCIS (Netherlands)

    Wolfs, Tom F W; Wagenaar, Jaap A; Niesters, Hubert G M; Osterhaus, Albert D M E

    2002-01-01

    We isolated Cowpox virus (CPXV) from the ulcerative eyelid lesions of a 14-year-old girl, who had cared for a clinically ill wild rat that later died. CPXV isolated from the rat (Rattus norvegicus) showed complete homology with the girl's virus. Our case is the first proven rat-to-human transmission

  13. Bile secretion in albino rat following chronic honey intake | Alagwu ...

    African Journals Online (AJOL)

    This study was carried out to evaluate the effect of honey intake on bile secretion, bile electrolytes, bilirubin and cholesterol levels including plasma cholesterol in albino rats. 20 male albino rats (200-210g) were used in the study. The rats were assigned randomly into 2 groups (control and honey-fed groups), each group ...

  14. Haematological Indices, Blood glucose levels and lipid profile of rats ...

    African Journals Online (AJOL)

    This work was done as a part of safety assessment to determine the effects of Tartrazine E102 on some haematological indices, glucose levels and blood lipid profile in rats. An animal model was used as a basis for interpreting the situation in humans. Consequently, 40 albino rats were divided into 5 groups of 8 rats each.

  15. Embryotoxicity and teratogenicity study with neohesperidin dihydrochalcone in rats

    NARCIS (Netherlands)

    Waalkens-Berendsen, D.H.; Kuilman-Wahls, M.E.M.; Bär, A.

    2004-01-01

    The embryotoxicity/teratogenicity of neohesperidin dihydrochalcone (NHDC) was examined in Wistar Crl:(WI)WU BR rats. NHDC was fed at dietary concentrations of 0, 1.25, 2.5 or 5 to groups of 28 mated female rats from day 0 to 21 of gestation. At Cesarean section 25, 22, 23, and 23 rats were found to

  16. Activation of peripheral leukocytes in rat pregnancy and experimental preeclampsia

    NARCIS (Netherlands)

    Faas, MM; Schuiling, GA; Linton, EA; Sargent, IL; Redman, CWG

    OBJECTIVE: The aim of this study was to search for activation markers of peripheral leukocytes in experimental preeclampsia in the rat. STUDY DESIGN: Experimental preeclampsia was induced in 14-day-pregnant rats by infusion of endotoxin (1.0 mu g/kg body weight). For comparison, rats with normal

  17. Diet induced gene expression in rat peripheral blood mononuclear cells

    NARCIS (Netherlands)

    Caimari, A.; Oliver, P.; Rodenburg, W.; Keijer, Jaap; Palou, A.

    2009-01-01

    Gene expression of rat peripheral blood mononuclear cells was analyzed by microarray analysis in normoweight and in diet-induced obese rats (cafeteria rats). The aim of this study was to identify genes involved in energy homeostasis that are altered in the obese state.

  18. EVALUATION OF PERFLUOROOCTANE SULFONATE (PFOS) IN THE RAT BRAIN

    Science.gov (United States)

    This study examined whether there is a differential distribution of PFOS within the brain, and compares adult rats with neonatal rats at an age when formation of the blood-brain barrier is not yet complete (postnatal day 7). Male and female Sprague-Dawley rats (60-70 day old, 4/...

  19. Honey increases sperm count in male albino rats by enhancing ...

    African Journals Online (AJOL)

    We investigated the effects of different doses of honey (H) and testosterone (T) on sperm count and reproductive hormones in male albino rats. Thirty-five male albino rats were randomly divided in a blinded fashion into 7 groups of 5 rats each. Group 1 (control) was given 0.2 ml of distilled water. Groups 2, 3 and 4 were ...

  20. EEG differences between the opioid and adrenergic psyhoneuroendocrine rat types

    DEFF Research Database (Denmark)

    Cristea, A; Moldovan, M; Munteanu, A M

    2000-01-01

    (BEA) of the "O" and "A" rat types during restrained wakefulness and anesthesia with Ether and chloral hydrate (CHL). The differentiation of the psyhoneuroendocrine rat types was made using the level of painful sensitivity. 13 hypersensitive "A" and 14 hyposensitive "O" rats were selected from a 91...

  1. Using giant African pouched rats to detect tuberculosis in human ...

    African Journals Online (AJOL)

    Giant African pouched rats previously have detected tuberculosis (TB) in human sputum samples in which the presence of TB was not initially detected by smear microscopy. Operant conditioning principles were used to train these rats to indicate TB-positive samples. In 2010, rats trained in this way evaluated 26,665 ...

  2. Parathyroid hormone dependent T cell proliferation in uremic rats

    DEFF Research Database (Denmark)

    Lewin, E; Ladefoged, Jens; Brandi, L

    1993-01-01

    was normalized. Rat PTH 1-84 stimulated in vitro the PHA-induced proliferation of T cells in a dose dependent manner. This effect was significant in CRF rat lymphocytes, but not in lymphocytes obtained from normal rats. Based upon the present results it is suggested that the secondary hyperparathyroidism...

  3. ( Cola Nitida Rubra ) on Reproductive Hormones in Rats

    African Journals Online (AJOL)

    Our previous study suggests that aqueous extract of kola nut had effect on reproductive hormones in male rats. This study evaluates the effects of kola nut extract on plasma level of testosterone and luteinizing hormones in male rats. 30 adult male rats were used. These were divided into three groups: group A served as ...

  4. histological changes in the lungs of adult wistar rats following

    African Journals Online (AJOL)

    Sixteen adult male Wistar rats of 9 weeks old weighing between 130-160 g were used for the study. They were obtained from the animal house of the Department of Anatomy, University of. Ilorin, Nigeria. The rats were kept in well- ventilated conditions in the animal house of the. Department of Anatomy and given normal rat.

  5. 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)

  6. Immature rats show ovulatory defects similar to those in adult rats lacking prostaglandin and progesterone actions

    Directory of Open Access Journals (Sweden)

    Sanchez-Criado Jose E

    2004-09-01

    Full Text Available Abstract Gonadotropin-primed immature rats (GPIR constitute a widely used model for the study of ovulation. Although the equivalence between the ovulatory process in immature and adult rats is generally assumed, the morphological and functional characteristics of ovulation in immature rats have been scarcely considered. We describe herein the morphological aspects of the ovulatory process in GPIR and their response to classical ovulation inhibitors, such as the inhibitor of prostaglandin (PG synthesis indomethacin (INDO and a progesterone (P receptor (PR antagonist (RU486. Immature Wistar rats were primed with equine chorionic gonadotropin (eCG at 21, 23 or 25 days of age, injected with human chorionic gonadotropin (hCG 48 h later, and sacrificed 16 h after hCG treatment, to assess follicle rupture and ovulation. Surprisingly, GPIR showed age-related ovulatory defects close similar to those in adult rats lacking P and PG actions. Rats primed with eCG at 21 or 23 days of age showed abnormally ruptured corpora lutea in which the cumulus-oocyte complex (COC was trapped or had been released to the ovarian interstitum, invading the ovarian stroma and blood and lymphatic vessels. Supplementation of immature rats with exogenous P and/or PG of the E series did not significantly inhibit abnormal follicle rupture. Otherwise, ovulatory defects were practically absent in rats primed with eCG at 25 days of age. GPIR treated with INDO showed the same ovulatory alterations than vehicle-treated ones, although affecting to a higher proportion of follicles. Blocking P actions with RU486 increased the number of COC trapped inside corpora lutea and decreased ovulation. The presence of ovulatory defects in GPIR, suggests that the capacity of the immature ovary to undergo the coordinate changes leading to effective ovulation is not fully established in Wistar rats primed with eCG before 25 days of age.

  7. Tryptophan depletion affects compulsive behaviour in rats

    DEFF Research Database (Denmark)

    Merchán, A; Navarro, S V; Klein, A B

    2017-01-01

    RATIONALE: Compulsive behaviour, present in different psychiatric disorders, such as obsessive-compulsive disorder, schizophrenia and drug abuse, is associated with altered levels of monoamines, particularly serotonin (5-hydroxytryptamine) and its receptor system. OBJECTIVES: The present study...... evaluated, as well as the 5-HT2A and 5-HT1A receptor binding, in different brain regions. METHODS: Wistar rats were selected as high (HD) or low (LD) drinkers according to their SIP behaviour, while Lister hooded rats did not show SIP acquisition. Both strains were fed for 14 days with either a TRP...... in the striatum was significantly reduced in the TRP-depleted HD Wistar rats. CONCLUSIONS: These results suggest that alterations of the serotonergic system could be involved in compulsive behaviour in vulnerable populations....

  8. Strychnine induces embryotoxicity in rat neurulation.

    Science.gov (United States)

    García-Alcocer, Guadalupe; Martínez-Torres, Ataúlfo; Miledi, Ricardo

    2005-01-01

    Administering strychnine, a potent antagonist of glycine receptors, to pregnant rats caused marked toxic effects on the ensuing embryos. The embryotoxic effects of strychnine were compared with those induced by retinal palmitate during rat neurulation; and it was found that strychnine was stronger than retinal palmitate in a number of abnormalities such as anencephaly, general aplasy and abnormal cerebral vesicles. Although the glycine receptor beta1 subunit mRNA was found to be expressed in the embryos when strychnine was administered to the mother rats, its presence may not fully account for the toxic effects and it may be that strychnine is targeting also other molecules, such as the nicotinic receptor that has been found early in development.

  9. Renal alterations in prediabetic rats with periodontitis

    DEFF Research Database (Denmark)

    Andersen, Carla Cruvinel Pontes; Holmstrup, Palle; Buschard, Karsten

    2008-01-01

    BACKGROUND: Periodontitis was shown to have an impact on glucose levels in prediabetic and diabetic rats. The Zucker fatty rat (ZFR) is a well-characterized model of prediabetes presenting with impaired glucose tolerance, hyperinsulinemia, dyslipidemia, and moderate hypertension. The aim...... of the present study was to investigate whether periodontitis influences kidney changes in ZFRs. METHODS: Male adult ZFRs (N = 19) and their lean littermates (N = 18) were studied. Periodontitis was induced with ligatures in half of the ZFRs and lean rats, whereas the other half served as controls. After 4 weeks...... IValpha1, fibronectin, and nephrin. Urinary albumin excretion and creatinine clearance were also evaluated. RESULTS: In prediabetic ZFRs, periodontitis was associated with kidney hypertrophy (P = 0.03) and a tendency for increased glomerular volume (P = 0.06). In lean littermates, elevated fibronectin m...

  10. Iron appetite and latent learning in rats.

    Science.gov (United States)

    Woods, S C; Vasselli, J R; Milam, K M

    1977-11-01

    Two experiments are reported which show that rats are capable of forming an association between the presence of iron in a solution when it is not specifically needed and a subsequent state of iron deficiency. Specifically, rats were trained to lever press for water while thirsty. One group received ferrous ions in addition to the water. When these rats were subsequently rendered iron deficient, they lever pressed more under extinction conditions as a graded function of lower hemoglobin levels. Controls that either did not receive ferrous ions during training or received solutions other than ferrous solutions during training did not respond this way under extinction conditions. This is therefore a type of latent learning previously demonstrated only for sodium appetite.

  11. Helminth parasites in black rats (Rattus rattus) and brown rats (Rattus norvegicus) from different environments in the Netherlands

    NARCIS (Netherlands)

    Franssen, Frits; Swart, Arno; van Knapen, Frans; van der Giessen, Joke

    2016-01-01

    BACKGROUND: Rattus norvegicus (brown rat) and Rattus rattus (black rat) are known carriers of bacteria, viruses, and parasites of zoonotic and veterinary importance. Moreover, rats may play a role in the transmission of muscle larvae of the zoonotic nematode Trichinella spiralis to farm animals. We

  12. Periovulatory leukocyte infiltration in the rat ovary.

    Science.gov (United States)

    Oakley, Oliver R; Kim, HeyYoung; El-Amouri, Ismail; Lin, Po-Ching Patrick; Cho, Jongki; Bani-Ahmad, Mohammad; Ko, Chemyong

    2010-09-01

    Ovulation is preceded by intraovarian inflammatory reactions that occur in response to the preovulatory gonadotropin surge. As a main inflammatory event, leukocytes infiltrate the ovary and release proteolytic enzymes that degrade the extracellular matrix weakening the follicular wall, a required step for follicle rupture. This study aimed to quantitatively measure the infiltrating leukocytes, determine their cell types, and localize infiltration sites in the periovulatory rat ovary. Cycling adult and gonadotropin-stimulated immature rats were used as animal models. Ovaries were collected at five different stages of estrous cycle in the adult rats (diestrus, 1700 h; proestrus, 1500 h; proestrus, 2400 h; estrus, 0600 h; and metestrus, 1700 h) and at five different time points after superovulation induction in the immature rats (pregnant mare's serum gonadotrophin, 0 h; pregnant mare's serum gonadotrophin, 48 h; human chorionic gonadotropin, 6 h; human chorionic gonadotropin, 12 h; and human chorionic gonadotropin, 24 h). The ovaries were either dissociated into a single cell suspension for flow cytometric analysis or fixed for immunohistochemical localization of the leukocytes. Similar numbers of leukocytes were seen throughout the estrous cycle (approximately 500,000/ovary), except proestrus 2400 when 2-fold higher numbers of leukocytes were found (approximately 1.1 million/ovary). A similar trend of periovulatory rise of leukocyte numbers was seen in the superovulation-induced immature rat model, recapitulating a dramatic increase in leukocyte numbers upon gonadotropin stimulation. Both macrophage/granulocytes and lymphocytes were among the infiltrating leukocytes and were localized in the theca and interstitial tissues, where platelet-endothelial cell adhesion molecule-1 and intercellular adhesion molecule-1 may play roles in the transmigration of leukocytes, because their expressions correlates spatiotemporally with the infiltrating leukocytes. In addition, a

  13. Neutron irradiation of rat embryos in utero

    International Nuclear Information System (INIS)

    Vogel, H.H. Jr.

    1978-01-01

    In the rat radiation is most effective in producing congenital anomalies during the organ-forming period (days 9 to 13), which is approximately equivalent to the 14th to 50th days of human pregnancy. We have exposed female Sprague--Dawley rats on the 18th day of pregnancy to single whole-body doses of fission neutrons (20 to 150 rads). After 20 rads there was a small decrease in body weight which lasted from birth to weaning. During this period 9% of the irradiated rats died compared with 4% of the controls. After 50 rads, 65/275 (23.6%) of the rats died between birth and weaning, and the body-weight loss of the survivors was increased. After 100 rads, 62/133 (47%) died at birth or day 1 and 103/133 (77.4%) died before weaning. A large and significant decrease in body weight persisted in the survivors. After 150 rads of fission neutrons, all 95 rats died within 48 hr of birth. From cross-fostering experiments, we believe this is a direct effect of radiation on the embryos and not an indirect action through the mother or her milk. The LD 50 for the period from birth to weaning is approximately 75 rads of fission neutrons. Studies of organ weight were conducted daily for the first week after birth in an attempt to find the cause of radiation mortality. Body weight of the irradiated animals averaged only about one-half that of the controls. The liver, kidney, brain, and testes of the neutron-irradiated rats weighed significantly less than those of the controls. The weights of the spleen, lungs, duodenum, and stomach were decreased but not significantly. The bone marrow appeared depleted in the irradiated long bones, but the spleen maintained active hematopoiesis 1 to 2 months after neutron exposure

  14. [Vitamins in rat experimental diets].

    Science.gov (United States)

    Kodentsova, V M; Beketova, N A; Vrzhesinskaia, O A

    2012-01-01

    A comparison of full semisynthetic diets used in different laboratories has shown that its vitamin content covers physiological requirements of rats in these micronutrients. The significant fluctuations in group B vitamin concentrations may take place when one uses brewer's yeast as a source of these vitamins. A preliminary assessment of vitamin content in brewer's yeasts is required in this case. An essential contribution of basic components in diet vitamin content must be taken in consideration when one creates a vitamin-deficient diet. Casein contains substantial amounts of group B vitamins and vitamin D. Therefore decontamination of casein from water and / or fat-soluble vitamins or the use of commercial purified casein is required. Vegetable oils are usually used as a fatty component of a diet and they simultaneously serve as an additional source of vitamin E. A choice of naturally containing vitamin E oil as a fat component of a diet is crucial for the creating an alimentary deficiency of vitamin E. The content of fat-soluble vitamins in the diet of control group (group of comparison) and vitamin level in the diet of experimental group of animals must be equivalent in investigations with modified (quality and quantitative) fat diet component. Caloric restriction by simple reducing of food without increasing the amount of vitamins to an adequate level is incorrect. With these considerations in mind proper attention to the equivalence of vitamin content in the diet of animals in experimental and control groups should be paid during experiments scheduling. Otherwise, the studies carried out under deficient or excessive intake of vitamins can lead to incorrect interpretation of the results and difficulties in their comparison with the data obtained under different conditions.

  15. Immunity to Fasciola hepatica in the rat

    International Nuclear Information System (INIS)

    Armour, J.; Dargie, J.D.

    1974-01-01

    Experiments were carried out which demonstrated an acquired immunity to Fasciola hapatica in the rat. It was shown that this immunity could be transferred to recipients using either lymphoid cells or serum from infected donor rats. The extent of the protection obtained by cells appeared to be related to the quantity and persistence of the antigenic stimulus in the donor. Likewise, the degree of immunity conferred by immune serum was dependent upon the volume transferred. The significance of these results in relation to the mechanism of immunity to fascioliasis is discussed

  16. Nerve excitability in the rat forelimb

    DEFF Research Database (Denmark)

    Arnold, Ria; Moldovan, Mihai; Rosberg, Mette Romer

    2017-01-01

    a novel setup to explore the ulnar nerve excitability in rodents. We provide normative ulnar data in 11 adult female Long Evans rats under anaesthesia by comparison with tibial and caudal nerves. Additionally, these measures were repeated weekly on 3 occasions to determine the repeatability of these tests....... Results Nerve excitability assessment of ulnar nerve proved to be a longitudinally repeatable measure of axonal function mature in rats, as were measures in tibial and caudal nerves. Comparison with existing method: Ulnar nerve motor excitability measures were different from the caudal and tibial...

  17. Determinants of acetylcholine levels in aged rats

    International Nuclear Information System (INIS)

    Smith, D.O.

    1986-01-01

    This paper assesses the ACh content and release in aged rats. Levels of ACh were found to decrease in older animals. Possible reasons for this decline are also examined. Radiolabeled incubation medium was substitued for bath saline. The incubation medium consisted of the bath saline containing a known amount of unlabeled choline, tritium-methyl choline chloride, U- C 14 sucrose, and physostigmine. To determine thekinetics, choline uptake was measured after a 4-min incubation. Unlabled choline chloride and tritium-choline were added to the saline. the results of the study demonstrate an age-related decline in the amount of transmetter, ACh, in nerve terminals at the rat neuromuscular junction

  18. [Electromagnetic Shielding Alters Behaviour of Rats].

    Science.gov (United States)

    Temuryants, N A; Kostyuk, A S; Tumanyants, K N

    2015-01-01

    It has been found that long-term electromagnetic shielding (19 hours per day for 10 days) leads to an increase in the duration of passive swimming time in male rats, decrease the duration of active swimming in the "forced swim" test as well as decrease of libido. On the other hand animals kept under the "open field" conditions do not show significant deviations from their normal behavior. Therefore, one could conclude that moderate electromagnetic shielding causes a depression-like state in rats.

  19. Absorption of pentacaine from ulcerous rat stomach

    International Nuclear Information System (INIS)

    Tomcikova, O.; Babulova, A.; Durisova, M.; Trnovec, T.; Benes, L.

    1985-01-01

    Pentacaine is a local anaesthetic which exhibited positive effects on healing of model ulcers in the rat stomach. The in situ disappearance of pentacaine from the ulcerous and intact rat stomach was studied. Gastric ulcers were produced by oral administration of phenylbutazone (200 mg/kg) 3.5 h before absorption experiment. Pentacaine exhibited a biexponential decrease from the lumen of the stomach, the rate of which was essentially the same in both groups. The total amount of pentacaine absorbed was small because of extremly low absorption rate. (author)

  20. Neurotoxicity of topically applied hexachlorophene in the young rat.

    Science.gov (United States)

    Shuman, R M; Leech, R W; Alvord, E C

    1975-05-01

    Young rats 6 to 22 days of age are extremely susceptible to the neurotoxic effects of hexachlorophene given as a daily bath of undiluted antiseptic detergent containing 3% hexachlorophene (pHiso-Hex). At this age, most rats are clinically and histologically damaged by as few as two daily baths. Younger rats are relatively resistant, probably because they have less myelin to be affected; older rats cannot be poisoned by this route, probably because the more mature liver excretes the drug more effectively. Age-dose-response curves in rats are similar to those in humans. This experimental model is potentially useful in defining other characteristics of this drug.

  1. The oncogenic action of ionizing radiation on rat skin

    Energy Technology Data Exchange (ETDEWEB)

    Burns, F.J.

    1991-01-01

    Progress has occurred in several areas corresponding to the specific aims of the proposal: (1) Progression and multiple events in radiation carcinogenesis of rat skin as a function of LET; (2) cell cycle kinetics of irradiated rat epidermis as determined by double labeling and double emulsion autoradiography; (3) oncogene activation detected by in situ hybridization in radiation-induced rat skin tumors; (4) amplification of the c-myc oncogene in radiation-induced rat skin tumors as a function of LET; and (5) transformation of rat skin keratinocytes by ionizing radiation in combination with c-Ki-ras and c-myc oncogenes. 111 refs., 13 figs., 12 tabs.

  2. Rat fetuin: distribution of protein and mRNA in embryonic and neonatal rat tissues

    DEFF Research Database (Denmark)

    Terkelsen, O B; Jahnen-Dechent, W; Nielsen, Henrik

    1998-01-01

    functions of fetuin, we have studied its synthesis and distribution during the prenatal development of the rat with immunohistochemistry and in situ hybridization. We have isolated fetuin from rat serum and produced an antibody against this protein. In situ hybridization was performed using a 375...... protein, in the sense that the highest concentrations are found in serum and body fluids of embryos and fetuses. In order to elucidate possible biological functions of fetuin, we have studied its synthesis and distribution during the prenatal development of the rat with immunohistochemistry and in situ...... hybridization. We have isolated fetuin from rat serum and produced an antibody against this protein. In situ hybridization was performed using a 375-nucleotides-long digoxigenin-labeled riboprobe. Fetuin was unevenly distributed in all organ systems during development, with the most pronounced expression at E16...

  3. Defective renal calcium reabsorption in genetic hypercalciuric rats.

    Science.gov (United States)

    Tsuruoka, S; Bushinsky, D A; Schwartz, G J

    1997-05-01

    Idiopathic hypercalciuria is a frequent cause of calcium (Ca) containing kidney stones. We have previously shown that there is increased intestinal Ca absorption in selectively inbred genetic hypercalciuric stone forming (GHS) rats; however, excess Ca excretion persists when the rats are fed a low Ca diet indicating a defect in renal Ca reabsorption and/or increased bone resorption. To determine if GHS rats have a defect in renal Ca reabsorption we performed 14C-inulin clearance studies on parathyroidectomized female GHS and control (Ctl) rats. After three baseline collections, chlorothiazide (CTZ) or furosemide (FUR) was infused and three more collections were obtained. Both GFR and filtered load of Ca did not differ among the groups; however, fractional and absolute excretion (UcaV) of Ca was three times higher in GHS rats. The increased Ca excretion was not diminished by a low Ca diet. Urine flow rate nearly tripled in all rats after either FUR or CTZ. After CTZ, UcaV was decreased to a greater extent in GHS compared to Ctl rats. After FUR, UcaV was increased to a greater extent in Ctl rats compared to GHS rats. These data indicate that GHS rats have a defect in renal Ca reabsorption, in addition to increased intestinal Ca absorption. The effect of CTZ was greater, and that of FUR was smaller, in GHS compared with Ctl rats, suggesting that the defect in renal Ca handling might be at the level of the thick ascending limb.

  4. Rats demonstrate helping behavior toward a soaked conspecific.

    Science.gov (United States)

    Sato, Nobuya; Tan, Ling; Tate, Kazushi; Okada, Maya

    2015-09-01

    Helping behavior is a prosocial behavior whereby an individual helps another irrespective of disadvantages to him or herself. In the present study, we examined whether rats would help distressed, conspecific rats that had been soaked with water. In Experiment 1, rats quickly learned to liberate a soaked cagemate from the water area by opening the door to allow the trapped rat into a safe area. Additional tests showed that the presentation of a distressed cagemate was necessary to induce rapid door-opening behavior. In addition, it was shown that rats dislike soaking and that rats that had previously experienced a soaking were quicker to learn how to help a cagemate than those that had never been soaked. In Experiment 2, the results indicated that rats did not open the door to a cagemate that was not distressed. In Experiment 3, we tested behavior when rats were forced to choose between opening the door to help a distressed cagemate and opening a different door to obtain a food reward. Irrespective of how they learned to open the door, in most test trials, rats chose to help the cagemate before obtaining a food reward, suggesting that the relative value of helping others is greater than the value of a food reward. These results suggest that rats can behave prosocially and that helper rats may be motivated by empathy-like feelings toward their distressed cagemate.

  5. WTC rat has unique characteristics such as resistant to streptozotocin.

    Science.gov (United States)

    Nagaki, Yoshiaki; Ito, Koichi; Kuwahara, Masayoshi

    2016-12-01

    Because we found that WTC rats might be resistant to streptozotocin (STZ), we have elucidated the mechanisms of resistant to the diabetogenic effects of STZ in the WTC rats. Dose response to STZ was evaluated with glucose levels. No significant changes in glucose level to STZ administration were observed in WTC rats. Insulin secretion by suppling glucose was preserved in WTC rats even after STZ administration. Although there was no significant difference in gene expression of both GLUT2 and Kir6.2, which were involved in STZ resistance, between WTC rats and Wistar rats, the expression of metallothionein 2a in pancreas and liver to STZ administration of WTC rats was significantly higher than that of Wistar rats. Moreover, alloxan did not induce diabetes in WTC rats as same as STZ. These results suggest that WTC rats might have powerful antioxidant property to protect β cells in pancreas. Because the STZ-resistant property is very close characteristics to human beings, WTC rats will become a useful animal model in diabetic researches.

  6. Guanethidine-induced sympathectomy in the nude rat

    DEFF Research Database (Denmark)

    Juul, A; Juul, P; Christensen, H B

    1989-01-01

    Guanethidine sulphate 40 mg/kg was administered intraperitoneally daily for 14 days to normal Lewis rats and athymic nude rats of a Lewis background (rnu/rnu). Histological examination of the superior cervical ganglia demonstrated a pronounced chromatolysis of the neurones and a loss of the major...... part of the nerve cells accompanied by an increased number of small mononuclear inflammatory cells. The extent of chromatolysis and nerve cell death induced by guanethidine did not differ between normal and nude rats, whereas the increase of the number of mononuclear cells was lower in the nude rats...... than in the normal rats (163 and 268 per cent respectively of the saline treated controls, P less than 0.01). Since guanethidine induced nerve cell death in the T-cell deficient nude rat to the same extent as in normal rats, it is concluded, that the effect is caused by either a thymus...

  7. Effects of electromagnetic radiation on the hemorheology of rats

    Science.gov (United States)

    Huang, Zhiwei; Tian, Tian; Xiao, Bo; Li, Wen

    2017-01-01

    The current work examines the effects of electromagnetic radiation on the hemorheology to provide an experimental basis for radiation protection. Electromagnetic radiation was generated by a Helmholtz coil constructed from copper wire. There were six rats altogether: three rats in the experimental group, and three rats in the control group. The rats in the experimental group were continuously exposed to radiation for 10 hours every day, and rats in the control group remained in a normal environment. After 30 days, the characteristics of hemorheology of the two groups were compared. The average plasma viscosity, whole blood high shear velocity, and whole blood low shear viscosity were lower in rats in the experimental group than in rats in the control group, while the whole blood shear viscosity was higher in the experimental group than in the control group. Results suggest that long term exposure to electromagnetic radiation does have certain impacts on the cardiovascular system, deeming it necessary to take preventative measures.

  8. Ontogenetic aspects of thallium-induced nephrotoxicity in rats.

    Science.gov (United States)

    Appenroth, D; Tiller, S; Gambaryan, S; Winnefeld, K; Fleck, C; Bräunlich, H

    1996-01-01

    The effect of Tl2SO4 (Tl, 20 mg kg-1 body wt.) on renal function was investigated in 10- and 20-day-old rats. Nephrotoxic effects were evaluated by the determination of glomerular filtration rate, urinary volume, electrolyte and protein excretion, as well as by morphological investigations. In contrast to adult rats there were no morphological destructions in 10- and 20-day-old rats. Changes in renal function seemed to be less expressed in 10- and 20-day-old than in adult rats. The smaller nephrotoxicity in 10-day-old rats may be caused by lower Tl concentration in renal tissue, whereas in 20-day-old rats decreased nephrotoxicity cannot be explained in this way. The activity of Na+/K(+)-ATPase in rat renal tissues was found to be involved in the mechanisms of Tl enrichment in renal tissue, being an indirect determinant of Tl nephrotoxicity.

  9. Core temperature of tailless rats exposed to centrifugation

    Science.gov (United States)

    Monson, C. B.; Oyama, J.

    1984-01-01

    The role of the tail in the altered thermoregulation of rats during acute exposure to hypergravity was investigated, using groups of rats of two ages: 55 days (young) and 138 days (old). Rectal and foot temperature changes were measured in intact and tailless rats subjected to 1 h centrifugation of 2.8 G, with preceding (1 h) and following (1-3 h) 1 G periods. At 22 C, the loss of body heat from the tail per se does not measurably contribute to the hypothermia induced by hypergravity. However, the heat loss from the feet was greater in the tailless rats than in the intact rats from the young group of animals, although there was no significant difference between the tailless and intact rats in the old animal group. It is concluded that the inhibition of heat production is a significant factor in the hypothermia of centrifuged tailless rats, as it has been previously shown to be in the intact animals.

  10. Palmitoylated PrRP analog decreases body weight in DIO rats but not in ZDF rats

    Czech Academy of Sciences Publication Activity Database

    Holubová, Martina; Zemenová, Jana; Mikulášková, Barbora; Panajotová, V.; Stöhr, J.; Haluzík, M.; Kuneš, Jaroslav; Železná, Blanka; Maletínská, Lenka

    2016-01-01

    Roč. 229, č. 2 (2016), s. 85-96 ISSN 0022-0795 R&D Projects: GA ČR(CZ) GA15-08679S; GA TA ČR(CZ) TE01020028 Institutional support: RVO:61388963 Keywords : prolactin-releasing peptide * lipidization * diet-induced obesity * ZDF rats * food intake * rat Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 4.706, year: 2016

  11. Palmitoylated PrRP analog decreases body weight in DIO rats but not in ZDF rats

    Czech Academy of Sciences Publication Activity Database

    Holubová, M.; Zemenová, J.; Mikulášková, Barbora; Panajotová, V.; Stöhr, J.; Haluzík, M.; Kuneš, Jaroslav; Železná, B.; Maletínská, L.

    2016-01-01

    Roč. 229, č. 2 (2016), s. 85-96 ISSN 0022-0795 R&D Projects: GA TA ČR(CZ) TE01020028; GA ČR(CZ) GA15-08679S Institutional support: RVO:67985823 Keywords : prolactin-releasing peptide * lipidization * diet-induced obesity * ZDF rats * food intake rat Subject RIV: ED - Physiology Impact factor: 4.706, year: 2016

  12. Efficacy and Safety of Gwakhyangjeonggi-San Retention Enema in Normal Rats and Spontaneously Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Eunyoung Song

    2013-01-01

    Full Text Available The purpose of this study is to establish a protocol of retention-enema experiments and evaluate the antihypertensive effect and the safety of Gwakhyangjeonggi-san retention enema. Normal and spontaneously hypertensive rats (SHRs were divided into treatment and control groups, respectively. We applied the Gwakhyangjeonggi-san extract by decoction and 0.9% NaCl in each group, estimated the blood pressure and body weight, and performed HPLC analysis. ALT, AST, BUN, and creatinine were examined. The systolic blood pressure within each group in normal rats differed significantly in time effect, and so did the diastolic blood pressure in the treatment group of normal rats. The systolic, diastolic, and mean blood pressure showed significant differences in group effect in the treatment group of the SHRs. The time effect of the body weight in both groups of normal rats differed significantly, so did group × time and time effects in both groups of SHRs. AST, ALT, BUN, and creatinine showed no significant difference between groups. We concluded that the Gwakhyangjeonggi-san retention enema has a hypotensive effect in normal rats within the regular range of blood pressure, but an antihypertensive effect in SHRs. Also, the intervention is safe and does not affect the liver and kidney functions in normal rats.

  13. Prior access to a sweet is more protective against cocaine self-administration in female rats than male rats

    Science.gov (United States)

    Cason, Angie M.; Grigson, Patricia S.

    2013-01-01

    It is well established that female rats are more sensitive than male rats to the reinforcing effects of cocaine (Lynch, 2008 for review). We hypothesized that greater preference for cocaine would support greater avoidance of a cocaine-paired taste cue in female vs. male rats. Moreover, at least in male rats, greater avoidance of the taste cue is associated with greater cocaine self-administration (Grigson & Twining, 2002). Thus, we anticipated that female rats would not only demonstrate greater avoidance of the drug-paired taste cue, but greater drug-taking as well. We tested these hypotheses by examining avoidance of a saccharin cue in male and female rats following several pairings with self-administered saline or cocaine (0.16, 0.33, or 0.66 mg/infusion). Contrary to expectations, the results showed that female rats exhibited less avoidance of the cocaine-associated saccharin cue than male rats and self-administered less, rather than more, cocaine, Thus, while female rats reportedly take more drug than male rats when the drug is presented in the absence of an alternative reward, they take less drug than male rats when the opportunity to self-administer cocaine is preceded by access to a palatable sweet. Females, then, may not simply be more sensitive to the rewarding properties of drug, but also to the reinforcing properties of natural rewards and this increase in sensitivity to sweets may serve to protect against drug-taking behavior. PMID:23474135

  14. Serum testosterone concentration in chloroquine- treated rats ...

    African Journals Online (AJOL)

    ONOS

    2010-07-05

    Jul 5, 2010 ... The effects of ascorbic acid (vitamin C) and alpha-tocopherol (vitamin E) were studied on serum testosterone ... chloroquine are probably mediated via the generation of free radicals. ... Effects of ascorbic acid and alpha-tocopherol on serum testosterone concentration in chloroquine-treated rats. Groups.

  15. Voluntary Oral Administration of Losartan in Rats.

    Science.gov (United States)

    Diogo, Lucília N; Faustino, Inês V; Afonso, Ricardo A; Pereira, Sofia A; Monteiro, Emília C; Santos, Ana I

    2015-09-01

    Gavage is a widely performed technique for daily dosing in laboratory rodents. Although effective, gavage comprises a sequence of potentially stressful procedures for laboratory animals that may introduce bias into experimental results, especially when the drugs to be tested interfere with stress-dependent parameters. We aimed to test vehicles suitable for drug delivery by voluntary ingestion in rats. Specifically, Male Wistar rats (age, 2 to 3 mo) were used to test nut paste (NUT), peanut butter (PB), and sugar paste (SUG) as vehicles for long-term voluntary oral administration of losartan, an angiotensin II receptor blocker. Vehicles were administered for 28 d without drug to assess effects on the glucose level and serum lipid profile. Losartan was mixed with vehicles and either offered to the rats or administered by gavage (14 d) for subsequent quantification of losartan plasma levels by HPLC. After a 2-d acclimation period, all rats voluntarily ate the vehicles, either alone or mixed with losartan. NUT administration reduced blood glucose levels. The SUG group had higher concentrations of losartan than did the gavage group, without changes in lipid and glucose profiles. Our results showed that NUT, PB, and SUG all are viable for daily single-dose voluntary ingestion of losartan and that SUG was the best alternative overall. Drug bioavailability was not reduced after voluntary ingestion, suggesting that this method is highly effective for chronic oral administration of losartan to laboratory rodents.

  16. Monoclonal antibodies against rat leukocyte surface antigens

    NARCIS (Netherlands)

    van den Berg, T. K.; Puklavec, M. J.; Barclay, A. N.; Dijkstra, C. D.

    2001-01-01

    Monoclonal antibodies have proven to be powerful tools for studying the properties of leukocyte surface antigens and the cells that express them. In the past decades many monoclonal antibodies (mAb) for identifying the different rat leukocyte surface antigens have been described. A list of mAb is

  17. Transgenic Rat Models for Breast Cancer Research

    Science.gov (United States)

    1998-10-01

    mutations in the rat genome is suggested on the heels of the recent abilities to clone animals from somatic cells, as was the case for sheep named...34 Dolly " (32). In this approach one would generate the desired mutations by gene targeting in somatic cells that can be grown in culture. One cell clones

  18. induced cerebral injury in a rat model

    African Journals Online (AJOL)

    SDS-PAGE was used for the separation of proteins, after which samples were transferred to polyvinylidene fluoride (PVDF) membranes. Monoclonal rabbit antibodies against rat LC3 were used to label the tissue proteins, and thereafter, samples were rinsed with phosphate-buffered saline (PBS) solution with the detergent ...

  19. Swelling of rat hepatocytes stimulates glycogen synthesis

    NARCIS (Netherlands)

    Baquet, A.; Hue, L.; Meijer, A. J.; van Woerkom, G. M.; Plomp, P. J.

    1990-01-01

    In hepatocytes from fasted rats, several amino acids are known to stimulate glycogen synthesis via activation of glycogen synthase. The hypothesis that an increase in cell volume resulting from amino acid uptake may be involved in the stimulation of glycogen synthesis is supported by the following

  20. Toxicological investigation of diethylphthalate in rats

    NARCIS (Netherlands)

    Jansen EHJM; van den Ham WA; de Fluiter P; van Leeuwen FXR

    1993-01-01

    In a study in which male rats have been exposed to 0, 200, 600, 2000, 6000 and 20000 mg diethylphthalate (DEP)/kg diet for 2 weeks, body weight and liver weight and a number of enzyme parameters which are related with peroxisome proliferation (palmitoyl coenzyme-A oxidase (PCO), enoyl coenzyme-A

  1. Toxicological investigation of dibutylphthalate in rats

    NARCIS (Netherlands)

    Jansen EHJM; van den Ham WA; de Fluiter P; van Leeuwen FXR

    1993-01-01

    In a study in which male rats have been exposed to 0, 20, 60, 200, 600 and 2000 mg dibutylphthalate (DBP)/kg diet for 2 weeks, body weight and liver weight and a number of enzyme parameters which are related with peroxisome proliferation (palmitoyl coenzyme-A oxidase (PCO, enoyl coenzyme-A hydratase

  2. Lipogenesis in maintenance cultures of rat hepatocytes

    NARCIS (Netherlands)

    Geelen, Math J.H.; Gibson, David M.

    1975-01-01

    Induction of the several enzymes in the liver cytosol catalyzing de novo synthesis of fatty acids from glucose has been demonstrated in intact animals. When carbohydrate is provided to previously starved rats the metabolism of liver switches from a gluconeogenic-ketogenic economy to a

  3. Toluene depresses plasma corticosterone in pregnant rats

    DEFF Research Database (Denmark)

    Hougaard, K. S.; Hansen, A. M.; Hass, Ulla

    2003-01-01

    of corticosteroids from the maternal to the foetal compartment. Pregnant rats were subjected to either 1500 ppm toluene 6 hr/day and/or a schedule of "Chronic mild stress" during the last two weeks of gestation. Exposure to toluene was associated with reduced birth weight and lower maternal weight gain, the latter...

  4. Gastrointestinal absorption of Np in rats

    International Nuclear Information System (INIS)

    Wirth, R.; Volf, V.

    1985-01-01

    The effect of Np mass and the acidity of the administered Np solutions as well as the age, sex and nutritional status of the animals injected or gavaged with 239Np or 237Np were determined. The latter factor proved to be dominant for absorption of Np from the gut. Thus in fasting weanling and young adult male rats, the absorption of 239Np was sixfold higher (0.18% and 0.12%, respectively) than in fed ones (0.03% and 0.02%, respectively). Absorption by fasted adult females was 0.05% of the administered 239Np, about half of that of adult males. Raising the Np-mass gavaged to fasted female rats to 1 and 10 mg 237Np/kg resulted in an absorption of 0.23% and 0.26%, respectively. Thus, an increased absorption of Np in adult rats seems to be expected only if a large mass is ingested. No dependence of the absorption of Np on nitric acid concentration was found. The data obtained after oral administration of 238Pu and 239Np to adult rats suggest that the f1 factor recommended by the ICRP for fractional absorption of soluble Np compounds from the gut should be decreased, whereas the f1 factor for soluble Pu compounds should be raised

  5. A microculture technique for rat lymphocyte transformation.

    Science.gov (United States)

    Lindsay, V J; Allardyce, R A

    1979-01-01

    We report the development of an economical microculture technique suitable for measuring rat lymphocyte response to mitogens and in mixed lymphocyte reactions. The effects of varying culture conditions, i.e. source of serum, addition and concentration of 2-mercaptoethanol, mitogen concentrations, culture incubation times, absorption of serum, lymphocyte numbers and microtitre plate well shape are described.

  6. Aniracetam reverses memory impairment in rats.

    Science.gov (United States)

    Martin, J R; Moreau, J L; Jenck, F

    1995-02-01

    The pyrrolidinone derivative aniracetam given orally immediately after acquisition of an inhibitory avoidance response reproducibly ameliorated scopolamine-induced amnesia in female rats in an extensive series of test sessions conducted over a 1-year period. In a dose-response experiment it was demonstrated that 50 mg kg-1 was the lowest oral dose of aniracetam to significantly ameliorate scopolamine-induced amnesia. Combined results from these numerous test sessions demonstrated that 50 mg kg-1 aniracetam administered to scopolamine-treated rats resulted in 53% of the animals exhibiting correct passive avoidance responding in the retention evaluation versus 9% of the scopolamine-treated rats given vehicle (in comparison, 64% of the rats injected with vehicle rather than scopolamine in this experimental situation exhibited correct responding in the retention test). There was minimal variation in this pattern of results over the successive 1-month blocks constituting the complete experimental period. Thus, the nootropic compound aniracetam replicably exhibited memory enhancing effects in this animal model of reduced cholinergic function.

  7. Rat Lungworm Expands into North America

    Centers for Disease Control (CDC) Podcasts

    2016-01-21

    Emily York, integrated pest management specialist at the Sam Noble Museum of Natural History, discusses the rat lungworm expansion in North America.  Created: 1/21/2016 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 1/21/2016.

  8. Renin release from isolated rat glomeruli

    DEFF Research Database (Denmark)

    Skøtt, O; Baumbach, Lars Anders

    1981-01-01

    1. The effects of calcium deprivation and D600 on the rate of renin release and seasonal variations in the response were studied on juxtaglomerular cells from a preparation of isolated rat glomeruli superfused in vitro. 2. Reduction of superfusate calcium concentration caused an increase in renin...

  9. Circadian clock components in the rat neocortex

    DEFF Research Database (Denmark)

    Rath, Martin Fredensborg; Rohde, Kristian; Fahrenkrug, Jan

    2013-01-01

    in the rat neocortex. Among these, Per1, Per2, Per3, Cry1, Bmal1, Nr1d1 and Dbp were found to exhibit daily rhythms. The amplitude of circadian oscillation in neocortical clock gene expression was damped and the peak delayed as compared with the SCN. Lesions of the SCN revealed that rhythmic clock gene...

  10. Epidermal growth factor in the rat lung

    DEFF Research Database (Denmark)

    Raaberg, Lasse; Poulsen, Steen Seier; Nexø, Ebba

    1991-01-01

    of the rat from a couple of days prior to birth and throughout life. Further, we report EGF immunoreactivity to be present in cells in the bronchi and the bronchioles from day 20-21 of gestation and throughout life. G-200 gelchromatography of lung extracts indicates that the EGF-reactive material is a high...

  11. New isoforms of rat Aquaporin-4

    DEFF Research Database (Denmark)

    Moe, Svein Erik; Sorbo, Jan Gunnar; Søgaard, Rikke

    2008-01-01

    Aquaporin-4 (AQP4) is a brain aquaporin implicated in the pathophysiology of numerous clinical conditions including brain edema. Here we show that rat AQP4 has six cDNA isoforms, formed by alternative splicing. These are named AQP4a-f, where AQP4a and AQP4c correspond to the two classical M1 and M...

  12. Neuroglobin in the rat brain: localization

    DEFF Research Database (Denmark)

    Hundahl, Christian Ansgar; Allen, Gregg C; Nyengaard, Jens Randel

    2008-01-01

    in the rat brain using immunohistochemistry, in situ hybridization, and quantitative real-time PCR (qRT-PCR). This revealed the interesting finding that Ngb expression is restricted to a few neurone populations, many of which are involved in the sleep-wake cycle, circadian regulation or food regulation...

  13. Kinetics of glucose transport in rat muscle

    DEFF Research Database (Denmark)

    Ploug, Thorkil; Galbo, Henrik; Vinten, Jørgen

    1987-01-01

    The effects of insulin and prior muscle contractions, respectively, on 3-O-methylglucose (3-O-MG) transport in skeletal muscle were studied in the perfused rat hindquarter. Initial rates of entry of 3-O-MG in red gastrocnemius, soleus, and white gastrocnemius muscles as a function of perfusate 3-O...

  14. DNA isolation from rat tail or ear

    NARCIS (Netherlands)

    Cuppen, E.

    2010-01-01

    This protocol describes a rapid procedure for isolating DNA from rat tail or ear punches. The simplest version of the protocol can be scaled for use in 96-well (deep-well) plates. The quality of the DNA is sufficient for any polymerase chain reaction (PCR)-based genotyping approach.

  15. The rat incisor in toxicologic pathology

    NARCIS (Netherlands)

    Kuijpers, M.H.M.; Kooij, A.J. van de; Slootweg, P.J.

    1996-01-01

    Microscopic examination of the incisors of rats and mice may reveal toxicologically significant changes. First, the incisor morphology reflects the nutritional status of the animal: fluctuations of mineral metabolism and vitamin availability are disclosed by the rodent incisors, because the incisors

  16. Immunotoxicity of clonazepam in adult albino rats.

    Science.gov (United States)

    Rabei, Hanan Mostafa

    2013-01-01

    Clonazepam as an addictive drug is studied to elucidate its destructive effects on rats' immune system. The aim of the current work was to study the immunologic changes induced by sub-chronic administration of clonazepam for three weeks followed by a withdrawal period in adult male albino rats. Seventy-two Sprague Dawley rats were divided into three equal groups. The first group was used as control; the second and third groups were treated with clonazepam. Six rats from each group were sacrificed weekly. Data showed that clonazepam induced a significant suppression in the level of IFN-gamma cortisol production, total splenocytes count and lymphocytes transformation induced by PHA mitogen along the experimental period especially in the third group. However, subchronic doses of clonazepam increased the production of IL-10 in both treated groups. Moreover, significant DNA damage in the peripheral blood lymphocytes of both treated groups was observed along the duration of the study. In conclusion, the immune system responses can be adversely affected to a greater extent by sub-chronic administration of clonazepam and should be prescribed cautiously as patients may turn addict to it.

  17. Prenatal Caffeine Exposure Impairs Pregnancy in Rats

    Directory of Open Access Journals (Sweden)

    Maryam Yadegari

    2016-12-01

    Full Text Available Background: In recent years, concerns have been raised about human reproductive disorders. Caffeine consumption is increasing by the world’s population and there is a relationship between caffeine intake and adverse reproductive outcomes. The aim of this study was to evaluate the effects of caffeine on implantation sites, number of live births, birth weight, crown-rump length (CRL and abnormality in pregnant rats. Materials and Methods: In this experimental study, 40 female albino rats (170-190 g were randomly divided into two experimental and two control groups (n=10/each group. In both experimental groups, animals received caffeine intraperitoneally (IP: 150 mg/kg/day on days 1-5 of pregnancy. In experimental group 1, treated animals were euthanized on day 7of pregnancy and the number of implantation sites was counted. In experimental group 2, treated animals maintained pregnant and after delivery, the number of live births, birth weight, CRL and abnormality of neonates were investigated. In control group, animals received IP injections of distilled water. Data were analyzed by independent t test. Results: Results showed that administration of caffeine significantly decreased the number of implantation sites, number of live births and CRL as compared with control group (P<0.05. There were no significant differences regarding birth weight and abnormality of neonate rats between experimental and control groups. Conclusion: These results suggest that caffeine caused anti-fertility effect and significantly decreased CRL in neonate rats.

  18. Oxytocin biotransformation in the rat limbic brain

    NARCIS (Netherlands)

    Burbach, J.P.H.; Schotman, P.; Kloet, E.R. de

    2006-01-01

    Two peptide fragments of oxytocin were isolated by high-pressure liquid chromatography from digests of oxytocin obtained after exposure to a SPM preparation of the rat limbic brain. The structures of these peptides, being Gln-Asn-Cys(O)x-Pro-Leu-GlyNH2 and Gln-Asn-Cys(-S-S-Cys)-Pro-Leu-GlyNH2, were

  19. Sequential causal learning in humans and rats

    NARCIS (Netherlands)

    Lu, H.; Rojas, R.R.; Beckers, T.; Yuille, A.; Love, B.C.; McRae, K.; Sloutsky, V.M.

    2008-01-01

    Recent experiments (Beckers, De Houwer, Pineño, & Miller, 2005;Beckers, Miller, De Houwer, & Urushihara, 2006) have shown that pretraining with unrelated cues can dramatically influence the performance of humans in a causal learning paradigm and rats in a standard Pavlovian conditioning paradigm.

  20. In Utero Hepatocellular Transplantation in Rats

    Directory of Open Access Journals (Sweden)

    Emma Muñoz-Sáez

    2013-01-01

    Full Text Available This work represents a step forward in the experimental design of an in utero hepatocellular transplantation model in rats. We focused on the enrichment optimization of isolated fetal hepatocytes suspension, arranging the surgery methodology of in utero transplantation, monitoring the biodistribution of the transplanted hepatocytes, and assessing the success of the transplants. Rat fetuses have been transplanted at the 17th embryonic day (ED17 with fetal hepatocytes isolated from rats at the end of pregnancy (ED21. We assessed possible differences between lymphocyte population, CD4 positive, CD8 positive, double-positive T-cells, and anti-inflammatory cytokines interleukins 4 and 10 (IL4 and IL10 as well. Cellular viability reached the rates of 90–95%. Transplanted groups had a limited success. Transplanted hepatocytes were not able to pass through the hematoplacental barrier. The hepatocytes injected were primarily located in the liver. There was an upward trend in the whole amount of T CD4 and T CD8 cells. There was an increased IL4 in the transplanted groups observed in the pregnant rats. The possibility to induce tolerance in fetuses with a hepatocyte transplant in utero could be a key point to avoid the immunosuppression treatments which must be undergone by transplanted patients.

  1. Rat pro-opiomelanocortin contains sulfate

    Energy Technology Data Exchange (ETDEWEB)

    Hoshina, H.; Hortin, G.; Boime, I.

    1982-07-02

    Intermediate lobes isolated from rat pituitary glands incorporated (/sup 35/S)sulfate into pro-opiomelanocortin and other adrenocorticotropic hormone-containing peptides. Incubation of intermediate lobes in medium containing the arginine analog canavanine inhibited the cleavage of pro-opiomelanocortin into smaller products. Pro-opiomelanocortin that accumulated in the presence of canavanine was also sulfated.

  2. Taurine content of tissues of irradiated rats

    International Nuclear Information System (INIS)

    Akhalaya, M.Ya.; Bogatyrev, G.P.; Kudryashov, Yu.B.; Yartsev, E.I.

    1976-01-01

    The taurine content of tissues (liver, stomach, small intestine and spleen) of rats irradiated with doses of 700 and 450 rads has been studied. Phase changes have been found in the taurine content of radiosensitive tissues in the course of radiation injury development

  3. Behavioral effects of etiracetam in rats

    NARCIS (Netherlands)

    Wolthuis, O.L.

    1981-01-01

    The effects of etiracetam, a structural analogue or piracetam, were investigated in rats on Y-maze discrimination acquisition, on open field behavior, on one-trial passive avoidance learning and on shuttlebox acquisition and extinction. The results indicate that this drug significantly enhances

  4. Following Exhaustive Exercise in Male Rats

    Directory of Open Access Journals (Sweden)

    reza Badalzadeh

    2014-12-01

    Conclusion: Long-term treatment of rats with cinnamon and regular training improved cardiac hemodynamic through an additive effect. The positive effects of cinnamon and regular training on cardiac function were associated with a reduced serum MDA level and an improved blood lipid profile.

  5. Disposition of hexobarbital enantiomers in the rat

    NARCIS (Netherlands)

    van der Graaff, M; Vermeulen, N P; Joeres, R P; Breimer, D D

    1983-01-01

    The enantiomers of hexobarbital (HB), designated as (+)-HB and (-)-HB, were administered orally to separate groups of rats. Blood concentration-time curves of the parent compounds and the metabolites 3'-hydroxyhexobarbital (OH-HB) and 3'-ketohexobarbital (K-HB) were determined, as well as the

  6. Haematobiochemical Changes In Albino Rats Infected With ...

    African Journals Online (AJOL)

    Some haematological and biochemical implications of Trypanosoma brucei infection was studied using Wistar albino rats. The haematological parameters studied are the white blood cell (WBC) count, which was used as an index of the presence and level of infection, and packed cell volume (PCV) which was used as an ...

  7. Motor development after vestibular deprivation in rats

    NARCIS (Netherlands)

    Geisler, HC; Gramsbergen, A

    This review summarizes the postural development in the rat and the influences of vestibular deprivation from the 5th postnatal day on this development. Vestibular deprivation leads to a delay in motor development. Most probably this delay is caused by a delay in the development of postural control,

  8. The adverse reaction of chitooligosaccharides in rats

    African Journals Online (AJOL)

    Yomi

    2012-01-31

    Jan 31, 2012 ... (New Zealand), Fermentation Cordyceps Powder was purchased from Institute of Fungus Resources, Guizhou University. (Guiyang, China). Silica gel plate was provided by Branch of Qing- dao Haiyang Chemical Co. (Qingdao, China). Experimental animals. Adult male Sprague-Dawley rats (180-200 g) ...

  9. Pulmonary cryptococcosis induces chitinase in the rat

    Directory of Open Access Journals (Sweden)

    Casadevall Arturo

    2008-05-01

    Full Text Available Abstract Background We previously demonstrated that chronic pulmonary infection with Cryptococcus neoformans results in enhanced allergic inflammation and airway hyperreactivity in a rat model. Because the cell wall of C. neoformans consists of chitin, and since acidic mammalian chitinase (AMCase has recently been implicated as a novel mediator of asthma, we sought to determine whether such infection induces chitinase activity and expression of AMCase in the rat. Methods We utilized a previously-established model of chronic C. neoformans pulmonary infection in the rat to analyze the activity, expression and localization of AMCase. Results Our studies indicate that intratracheal inoculation of C. neoformans induces chitinase activity within the lung and bronchoalveolar lavage fluid of infected rats. Chitinase activity is also elicited by pulmonary infection with other fungi (e.g. C. albicans, but not by the inoculation of dead organisms. Enhanced chitinase activity reflects increased AMCase expression by airway epithelial cells and alveolar macrophages. Systemic cryptococcosis is not associated with increased pulmonary chitinase activity or AMCase expression. Conclusion Our findings indicate a possible link between respiratory fungal infections, including C. neoformans, and asthma through the induction of AMCase.

  10. Extracellular ATP induces albuminuria in pregnant rats

    NARCIS (Netherlands)

    Faas, M.M.; van der Schaaf, G.; Borghuis, T.; Jongman, R.M.; van Pampus, Maria; de Vos, P.; van Goor, Harry; Bakker, W.W.

    BACKGROUND: As circulating plasma ATP concentrations are increased in pre-eclampsia, we tested whether increased plasma ATP is able to induce albuminuria during pregnancy. METHODS: Pregnant (day 14) and non-pregnant rats were infused with ATP (3000 microg/kg bw) via a permanent jugular vein cannula.

  11. in Alloxan-induced Diabetic Rats

    African Journals Online (AJOL)

    HP

    extract of its leaves [7,8]. Despite the fact that ethanolic extract of Carica papaya leaf is used in the treatment of diabetes in Nigeria [6], there is dearth of information on its efficacy. Therefore, this study was aimed at evaluating the anti- diabetic effect of ethanolic extract of Carica papaya leaves in alloxan-induced diabetic rats.

  12. Whey protein concentrate and dexamethasone protected rat ...

    African Journals Online (AJOL)

    Rat brains were fixed in 10% formalin, processed with routine paraffin wax techniques and stained with Haematoxylin and Eosin. Histomorphometric studies showed that radiation significantly (p< 0.05) reduced the thickness of both the molecular and granular layers of the cerebellum when compared with the control group.

  13. Immunomagnetic isolation of fetal rat gonocytes

    NARCIS (Netherlands)

    van den Ham, R.; van Pelt, A. M.; de Miguel, M. P.; van Kooten, P. J.; Walther, N.; van Dissel-Emiliani, F. M.

    1997-01-01

    PROBLEM: An efficient method to obtain highly enriched populations of viable gonocytes from rat embryos at Day 18 and Day 20 postcoitum (pc) is described. METHOD: Single-cell suspensions with high cell yield were obtained by a collagenase/ trypsin digestion of the decapsulated testis. The gonocytes

  14. Baroreflex Function in Rats after Simulated Microgravity

    Science.gov (United States)

    Hasser, Eileen M.

    1997-01-01

    Prolonged exposure of humans to decreased gravitational forces during spaceflight results in a number of adverse cardiovascular consequences, often referred to as cardiovascular deconditioning. Prominent among these negative cardiovascular effects are orthostatic intolerance and decreased exercise capacity. Rat hindlimb unweighting is an animal model which simulates weightlessness, and results in similar cardiovascular consequences. Cardiovascular reflexes, including arterial and cardiopulmonary baroreflexes, are required for normal adjustment to both orthostatic challenges and exercise. Therefore, the orthostatic intolerance and decreased exercise capacity associated with exposure to microgravity may be due to cardiovascular reflex dysfunction. The proposed studies will test the general hypothesis that hindlimb unweighting in rats results in impaired autonomic reflex control of the sympathetic nervous system. Specifically, we hypothesize that the ability to reflexly increase sympathetic nerve activity in response to decreases in arterial pressure or blood volume will be blunted due to hindlimb unweighting. There are 3 specific aims: (1) To evaluate arterial and cardiopulmonary baroreflex control of renal and lumbar sympathetic nerve activity in conscious rats subjected to 14 days of hindlimb unweighting; (2) To examine the interaction between arterial and cardiopulmonary baroreflex control of sympathetic nerve activity in conscious hindlimb unweighted rats; (3) to evaluate changes in afferent and/or central nervous system mechanisms in baroreflex regulation of the sympathetic nervous system. These experiments will provide information related to potential mechanisms for orthostatic and exercise intolerance due to microgravity.

  15. seed on haematological parameters of albino rats

    African Journals Online (AJOL)

    Dr Ejere

    2015-06-23

    Jun 23, 2015 ... animals for oral administration. Procurement and management of experimental animals. Forty-eight (48) adult male albino rats weighing between 150 to 250 g were obtained from the Genetics and Animal breeding Laboratory of the Department of Zoology and Environmental Biology,. University of Nigeria ...

  16. Effect of orlistat on fat absorption in rats: A comparison of normal rats and rats with diverted bile and pancreatic juice

    DEFF Research Database (Denmark)

    Porsgaard, Trine; Straarup, Ellen Marie; Mu, Huiling

    2003-01-01

    this with the transport in normal rats and rats with fat malabsorption. Rats were subjected to cannulation of the main mesenteric lymph duct, and a feeding catheter was inserted into the stomach. In addition, malabsorbing rats were cannulated in the common bile and pancreatic duct. Emulsified safflower, fish...... and furthermore that the source of fat had no influence on the inhibitory effect of orlistat. Orlistat did not interfere with the absorption of the hydrolysis products, since high absorption of sn-2 MAG and FFA (oleic acid) mixed with orlistat was observed. The baseline lymphatic transport in the orlistat group...

  17. Evaluation of Jet Fuel and Noise-Induced Hearing Loss in Rats (Rattus norvegicus)

    Science.gov (United States)

    2014-05-13

    rats served as subjects in the first study and eighty albino Fischer 344 rats were used in the second study. Half the animals were males and the...other strains of rats, such as the albino Fischer 344 rat, the pigmented Long-Evans rat is generally more resistant to ototoxicity. Therefore, higher

  18. Effect of dietary soy isoflavones on bone loss in ovariectomized rats ...

    African Journals Online (AJOL)

    Purpose: To determine the effect of dietary soy isoflavone supplementation on bone loss in ovariectomized (OVX) rats. Methods: Forty-eight rats were assigned randomly to groups of OVX rats receiving soy isoflavones (20, 30, or 40 mg/kg of body weight daily), untreated OVX rats, or untreated intact rats. After 8 weeks, bone ...

  19. Helminth parasites in black rats (Rattus rattus and brown rats (Rattus norvegicus from different environments in the Netherlands

    Directory of Open Access Journals (Sweden)

    Frits Franssen

    2016-05-01

    Full Text Available Background: Rattus norvegicus (brown rat and Rattus rattus (black rat are known carriers of bacteria, viruses, and parasites of zoonotic and veterinary importance. Moreover, rats may play a role in the transmission of muscle larvae of the zoonotic nematode Trichinella spiralis to farm animals. We aimed to study the intestinal and intramuscular helminths in wild rats from three different environments to assess the relevance of rats as carrier of zoonotic parasites for public health. Materials and methods: Wild brown rats (117 individuals and black rats (44 individuals were captured at farms, in suburban and in rural environments in the Netherlands. Intestinal helminths were isolated and identified morphologically. Artificial digestion was used to isolate muscle larvae. Results and discussion: Morphological analysis of rat intestinal contents yielded six nematode species (Syphacia muris, Heterakis spumosa, Aonchotheca murissylvatici, Trichuris muris, Nippostrongylus brasiliensis, and Strongyloides sp., three cestode species (Hymenolepis diminuta, H. nana and Hymenolepis (=Rodentolepis fraterna, and four trematode species (Plagiorchis muris, Plagiorchis proximus, Echinostoma chloropodis, and Notocotylus imbricatus.Black rats at farms displayed the lowest intestinal helminth species variation (six species and carried overall on average 0.93 species simultaneously. In comparison, brown rats at farms carried seven helminth species and 1.91 species simultaneously. Brown rats from suburban environments displayed the highest species variation (11 species at 1.82 simultaneous helminth species. Absence of trematodes from rats at farms may suggest limited exchange of rats between farms and surrounding wet rural environments. We report four species of veterinary (Syphacia muris or zoonotic relevance (Hymenolepis diminuta, Hymenolepis nana and Plagiorchis muris. We did not find Trichinella muscle larvae, consistent with long-term prevalence in Dutch wild rats.

  20. Cerebral microbleeds in a neonatal rat model.

    Directory of Open Access Journals (Sweden)

    Brianna Carusillo Theriault

    Full Text Available In adult humans, cerebral microbleeds play important roles in neurodegenerative diseases but in neonates, the consequences of cerebral microbleeds are unknown. In rats, a single pro-angiogenic stimulus in utero predisposes to cerebral microbleeds after birth at term, a time when late oligodendrocyte progenitors (pre-oligodendrocytes dominate in the rat brain. We hypothesized that two independent pro-angiogenic stimuli in utero would be associated with a high likelihood of perinatal microbleeds that would be severely damaging to white matter.Pregnant Wistar rats were subjected to intrauterine ischemia (IUI and low-dose maternal lipopolysaccharide (mLPS at embryonic day (E 19. Pups were born vaginally or abdominally at E21-22. Brains were evaluated for angiogenic markers, microhemorrhages, myelination and axonal development. Neurological function was assessed out to 6 weeks.mRNA (Vegf, Cd31, Mmp2, Mmp9, Timp1, Timp2 and protein (CD31, MMP2, MMP9 for angiogenic markers, in situ proteolytic activity, and collagen IV immunoreactivity were altered, consistent with an angiogenic response. Vaginally delivered pups exposed to prenatal IUI+mLPS had spontaneous cerebral microbleeds, abnormal neurological function, and dysmorphic, hypomyelinated white matter and axonopathy. Pups exposed to the same pro-angiogenic stimuli in utero but delivered abdominally had minimal cerebral microbleeds, preserved myelination and axonal development, and neurological function similar to naïve controls.In rats, pro-angiogenic stimuli in utero can predispose to vascular fragility and lead to cerebral microbleeds. The study of microbleeds in the neonatal rat brain at full gestation may give insights into the consequences of microbleeds in human preterm infants during critical periods of white matter development.