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Localisation of [131I]MIBG in nude mice bearing SK-N-SH human neuroblastoma xenografts: effect of specific activity.

Vaidyanathan, G.; Friedman, H. S.; Keir, S. T.; Zalutsky, M. R.
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
Publicado em /05/1996 Português
Relevância na Pesquisa
16.05%
The biodistribution of no-carrier-added (n.c.a.) meta-[131I]iodobenzylguanidine ([131I]MIBG) and that prepared by the standard isotopic exchange method were compared in athymic mice bearing SK-N-SH human neuroblastoma xenografts. No advantage in tumour uptake was observed for the n.c.a. preparation. BALB/c nu/nu mice exhibited lower uptake in highly innervated normal tissues (heart and adrenals) than normal BALB/c mice. In another experiment, the distribution of n.c.a. [131I]MIBG in the absence or presence (3-9 micrograms) of MIBG carrier was determined. At both 4 h and 24 h, the heart uptake was reduced by a factor of 1.5 even at a dose of 3 micrograms MIBG. Tumour uptake was not significantly altered by various amounts of unlabelled MIBG at either time point.

3-[211At]astato-4-fluorobenzylguanidine: a potential therapeutic agent with prolonged retention by neuroblastoma cells.

Vaidyanathan, G.; Zhao, X. G.; Larsen, R. H.; Zalutsky, M. R.
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
Publicado em //1997 Português
Relevância na Pesquisa
36.41%
An analogue of meta-iodobenzylguanidine (MIBG) in which an aromatic hydrogen was replaced with fluorine has been found to possess many properties similar to those of the parent compound. Moreover, 4-fluoro-3-iodobenzylguanidine (FIBG) was retained in vitro by human neuroblastoma cells to a much greater extent than MIBG itself. Since alpha-emitters such as 211At could be valuable for the treatment of micrometastatic disease, an FIBG analogue in which the iodine atom is replaced by 211At would be of interest. In this study, we have evaluated the in vitro and in vivo properties of 3-[211At]astato-4-fluorobenzylguanidine ([211At]AFBG). The specific binding of [211At]AFBG to SK-N-SH human neuroblastoma cells remained fairly constant over 2- to 3-log activity range and was similar to that of [131I]MIBG. The uptake of [211At]AFBG by this cell line was reduced by desipramine, ouabain, 4 degrees C incubation, noradrenaline, unlabelled MIBG and FIBG, suggesting that its uptake is specifically mediated through an active uptake-1 mechanism. Over the 16 h period studied, the amount of [211At]AFBG retained was similar to that of [131I]FIBG, whereas the per cent of retained meta-[211At]astatobenzylguanidine ([211At]MABG) was considerably less than that of [131I]FIBG (53% vs 75%; P < 0.05). The IC50 values for the inhibition of uptake of [131I]MIBG...

Potentiation of anti-cancer drug activity at low intratumoral pH induced by the mitochondrial inhibitor m-iodobenzylguanidine (MIBG) and its analogue benzylguanidine (BG)

Kuin, A; Aalders, M; Lamfers, M; Zuidam, D J van; Essers, M; Beijnen, J H; Smets, L A
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
Publicado em /02/1999 Português
Relevância na Pesquisa
26.36%
Tumour-selective acidification is of potential interest for enhanced therapeutic gain of pH sensitive drugs. In this study, we investigated the feasibility of a tumour-selective reduction of the extracellular and intracellular pH and their effect on the tumour response of selected anti-cancer drugs. In an in vitro L1210 leukaemic cell model, we confirmed enhanced cytotoxicity of chlorambucil at low extracellular pH conditions. In contrast, the alkylating drugs melphalan and cisplatin, and bioreductive agents mitomycin C and its derivative EO9, required low intracellular pH conditions for enhanced activation. Furthermore, a strong and pH-independent synergism was observed between the pH-equilibrating drug nigericin and melphalan, of which the mechanism is unclear. In radiation-induced fibrosarcoma (RIF-1) tumour-bearing mice, the extracellular pH was reduced by the mitochondrial inhibitor m-iodobenzylguanidine (MIBG) or its analogue benzylguanidine (BG) plus glucose. To simultaneously reduce the intracellular pH, MIBG plus glucose were combined with the ionophore nigericin or the Na+/H+ exchanger inhibitor amiloride and the Na+-dependent HCO3−/Cl−exchanger inhibitor 4,4′-diisothiocyanostilbene-2,2′-disulphonic acid (DIDS). Biochemical studies confirmed an effective reduction of the extracellular pH to approximately 6.2...

Increased survival of children with solid tumours: how did we get there and how to keep the success going?

Rechnitzer, Catherine
Fonte: e-Med Publicador: e-Med
Tipo: Artigo de Revista Científica
Publicado em 03/10/2011 Português
Relevância na Pesquisa
15.99%
Survival after childhood cancer has dramatically increased in the last 3 to 4 decades. Among extracranial tumours, Wilms tumours and other less common kidney tumours have the best results, but treatment of neuroblastoma, often disseminated at diagnosis, is still extremely challenging. How did survival of solid tumours in childhood increase from around 30% in the 1970s to 70–90% today? This is the result of a multidisciplinary effort and access to improved diagnostic techniques and treatment modalities. This article focuses on the role of imaging in this positive evolution and particularly, how imaging will contribute to keep the survival curves improving. Radiologists and other imaging experts retain a key position before diagnosis and during and after treatment. Investigations before diagnosis are key to further investigations and referral with no delay. The first investigations will most often involve radiologists through radiography or ultrasonography, according to tumour site. The description of these first observations and particularly the conclusion and its wording are crucial to the subsequent events leading to diagnosis. In imaging at diagnosis, the aim is to obtain a precise description of the primary tumour and its local spread as soon as possible. The choice of technique depends on local conditions but may include ultrasonography...

Catecholamine-secreting carotid body paraganglioma: successful preoperative control of hypertension and clinical symptoms using high-dose long-acting octreotide

Elshafie, Omayma; Al Badaai, Yahya; Alwahaibi, Khalifa; Qureshi, Asim; Hussein, Samir; Al Azzri, Faisal; Almamari, Ali; Woodhouse, Ncholas
Fonte: Bioscientifica Ltd Publicador: Bioscientifica Ltd
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
15.99%
A 48-year-old hypertensive and diabetic patient presented with a 10-year history of progressive right facial pain, tinnitus, hearing loss, sweating, and palpitations. Investigations revealed a 5.6 cm vascular tumor at the carotid bifurcation. Her blood pressure (BP) was 170/110, on lisinopril 20 mg od and amlodipine 10 mg od and 100 U of insulin daily. A catecholamine-secreting carotid body paraganglioma (CSCBP) was suspected; the diagnosis was confirmed biochemically by determining plasma norepinephrine (NE) level, 89 000 pmol/l, and chromogranin A (CgA) level, 279 μg/l. Meta-iodobenzylguanidine and octreotide scanning confirmed a single tumor in the neck. A week after giving the patient a trial of octreotide 100 μg 8 h, the NE level dropped progressively from 50 000 to 25 000 pmol/l and CgA from 279 to 25 μg/l. Treatment was therefore continued with labetalol 200 mg twice daily (bid) and long-acting octreotide-LA initially using 40 mg/month and later increasing to 80 mg/month. On this dose and with a reduced labetalol intake of 100 mg bid, BP was maintained at 130/70 and her symptoms resolved completely. CgA levels returned to normal in the first week and these were maintained throughout the 3 month treatment period. During tumor resection...

Cardioprotective Effect of Fimasartan, a New Angiotensin Receptor Blocker, in a Porcine Model of Acute Myocardial Infarction

Sim, Doo Sun; Jeong, Myung Ho; Song, Ho Chun; Kim, Jahae; Chong, Ari; Bom, Hee Seung; Jeong, In Seok; Oh, Sang Gi; Kim, Jong Min; Park, Dae Sung; Kim, Jung Ha; Lim, Kyung Seob; Kim, Min Suk; Ryu, Shi Hyun; Kim, Hyun Kuk; Kim, Sung Soo; Jang, Su Young; Cho
Fonte: The Korean Academy of Medical Sciences Publicador: The Korean Academy of Medical Sciences
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
15.99%
Cardioprotective effect of fimasartan, a new angiotensin receptor blocker (ARB), was evaluated in a porcine model of acute myocardial infarction (MI). Fifty swine were randomized to group 1 (sham, n=10), group 2 (no angiotensin-converting enzyme inhibitor [ACEI] or ARB, n=10), group 3 (perindopril 2 mg daily, n=10), group 4 (valsartan 40 mg daily, n=10), or group 5 (fimasartan 30 mg daily, n=10). Acute MI was induced by occlusion of the left anterior descending artery for 50 min. Echocardiography, single photon emission computed tomography (SPECT), and F-18 fluorodeoxyglucose cardiac positron emission tomography (PET) were performed at baseline, 1 week, and 4 weeks. Iodine-123 meta-iodobenzylguanidine (MIBG) scan was done at 6 weeks for visualization of cardiac sympathetic activity. Left ventricular function and volumes at 4 weeks were similar between the 5 groups. No difference was observed in groups 2 to 5 in SPECT perfusion defect, matched and mismatched segments between SPECT and PET at 1 week and 4 weeks. MIBG scan showed similar uptake between the 5 groups. Pathologic analysis showed similar infarct size in groups 2 to 5. Infarct size reduction was not observed with use of fimasartan as well as other ACEI and ARB in a porcine model of acute MI.

Cardiac 123I-MIBG uptake in de novo Brazilian patients with Parkinson's disease without clinically defined dysautonomia

Leite,Marco Antonio Araujo; Nascimento,Osvaldo J. M.; Pereira,João Santos; Amaral,Clayton; Mesquita,Cláudio T.; Azevedo,Jader C.; Brito,Adriana S. X. de; Pedras,Felipe Villela
Fonte: Academia Brasileira de Neurologia - ABNEURO Publicador: Academia Brasileira de Neurologia - ABNEURO
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/06/2014 Português
Relevância na Pesquisa
25.99%
Myocardial scintigraphy with meta-iodo-benzyl-guanidine (123I cMIBG) has been studied in Parkinson's disease (PD), especially in Asian countries, but not in Latin America. Most of these studies include individuals with PD associated to a defined dysautonomia. Our goal is to report the cardiac sympathetic neurotransmission in de novo Brazilian patients with sporadic PD, without clinically defined dysautonomia. We evaluated retrospectively a series of 21 consecutive cases with PD without symptoms or signs of dysautonomia assessed by the standard bedside tests. This number was reduced to 14 with the application of exclusion criteria. 123I cMIBG SPECT up-take was low or absent in all of them and the heart/mediastinum ratio was low in 12 of 14. We concluded that 123I cMIBG has been able to identify cardiac sympathetic neurotransmission disorder in Brazilian de novo PD patients without clinically defined dysautonomia.

Paraganglioma in a young patient with asymptomatic severe hypertension: a case report and review of the literature

Koumaras, Ch; Anagnostis, P; Tzimou, M; Giavanidis, I; Gossios, Th; Antoniadis, A; Athyros, V G; Karagiannis, A
Fonte: LITHOGRAPHIA Antoniadis I.-Psarras Th. G.P. Publicador: LITHOGRAPHIA Antoniadis I.-Psarras Th. G.P.
Tipo: Artigo de Revista Científica
Publicado em //2010 Português
Relevância na Pesquisa
15.99%
We present a case of a 19-year old woman who was admitted to our department with a recently, and incidentally, diagnosed severe hypertension [220/140 mmHg systolic/diastolic blood pressure (BP)]. The patient was asymptomatic. The laboratory investigation demonstrated both elevated plasma norepinephrine (1807 pg/ml, normal range 120-350 pg/ml) and 24h urinary free catecholamines (483 µg/24h, normal range <150 µg/24h), making the diagnosis of a catecholamineproducing tumor highly probable. Although magnetic resonance imaging of the abdomen showed normal adrenal glands, it revealed a mass (4x4 cm) anterior to the inferior vena cava. The diagnosis of paraganglioma was confirmed by the 131Imeta- iodobenzylguanidine scintigraphy. Preoperatively, α- and β-adrenergic receptor blockers were administered. After successful resection of the tumor, the patient's BP was restored to normal and remained stable during the 3-month follow up. Plasma and 24h urinary catecholamine levels were also normalized. In conclusion, it is important to consider paragangliomas as a possible cause of secondary hypertension and proceed to diagnosis and treatment as described above, since surgical removal of the tumor, especially in sporadic cases, may cure the patient.

Avaliação cardíaca com cintilografia com 123 I-mlBG e ventriculografia radioisotópica em pacientes submetidos à quimioterapia com antraciclinas na infância e adolescência; Cardiac scintigraphy evaluation with 123I-mIBG and radionuclide ventriculography in patients undergoing anthracycline chemotherapy in childhood and adolescence

Santos, Marcelo José dos
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 10/09/2015 Português
Relevância na Pesquisa
36.12%
INTRODUÇÃO: O câncer infantil é a primeira causa de morte em crianças, nos países desenvolvidos. Nos últimos 40 anos, graças ao desenvolvimento da Oncopediatria e de drogas como as antraciclinas (ATC), a taxa de cura tem atingido até 80%. Isto repercutiu em significativo aumento da sobrevida e, consequentemente, nos efeitos deletérios da quimioterapia com ATC, como a cardiotoxicidade. A fim de estudar os efeitos tardios da quimioterapia com ATC sobre o sistema nervoso cardíaco simpático (SNS), foi realizado estudo de cintilografia com 123I-mIBG (meta-iodobenzilguanedina ligado ao iodo123) e comparado com dose dos ATCs e fração de ejeção do ventrículo esquerdo (FEVE), através da ventriculografia radioisotópica (VR). As variáveis analisadas pela cintilografia com 123I-mIBG foram a relação coração/mediastino (C/M) e a taxa de clareamento (TC) que sinalizam o funcionamento neuronal cardíaco. MÉTODOS: realizado estudo transversal de pacientes assintomáticos submetidos à quimioterapia com ATC na infância e adolescência, com período de 2 a 21 anos, após o término do tratamento, e com ecocardiograma (ECO) normal. Dos 118 pacientes participantes recrutados, 27 foram excluídos (motivos: radioterapia torácica...

3-[211At]astato-4-fluorobenzylguanidine: a potential therapeutic agent with prolonged retention by neuroblastoma cells.

Vaidyanathan, G; Zhao, XG; Larsen, RH; Zalutsky, MR
Fonte: Universidade Duke Publicador: Universidade Duke
Tipo: Artigo de Revista Científica Formato: 226 - 233
Publicado em //1997 Português
Relevância na Pesquisa
56.59%
An analogue of meta-iodobenzylguanidine (MIBG) in which an aromatic hydrogen was replaced with fluorine has been found to possess many properties similar to those of the parent compound. Moreover, 4-fluoro-3-iodobenzylguanidine (FIBG) was retained in vitro by human neuroblastoma cells to a much greater extent than MIBG itself. Since alpha-emitters such as 211At could be valuable for the treatment of micrometastatic disease, an FIBG analogue in which the iodine atom is replaced by 211At would be of interest. In this study, we have evaluated the in vitro and in vivo properties of 3-[211At]astato-4-fluorobenzylguanidine ([211At]AFBG). The specific binding of [211At]AFBG to SK-N-SH human neuroblastoma cells remained fairly constant over 2- to 3-log activity range and was similar to that of [131I]MIBG. The uptake of [211At]AFBG by this cell line was reduced by desipramine, ouabain, 4 degrees C incubation, noradrenaline, unlabelled MIBG and FIBG, suggesting that its uptake is specifically mediated through an active uptake-1 mechanism. Over the 16 h period studied, the amount of [211At]AFBG retained was similar to that of [131I]FIBG, whereas the per cent of retained meta-[211At]astatobenzylguanidine ([211At]MABG) was considerably less than that of [131I]FIBG (53% vs 75%; P < 0.05). The IC50 values for the inhibition of uptake of [131I]MIBG...