Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 182
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Rehabilitation (Stuttg) ; 52(5): 329-36, 2013 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-23749615

RESUMO

AIM OF THE STUDY: We evaluated an occupation-related rehabilitation program, which has been designed to enhance the return to work of cancer patients. As return to work plays an important role to get back to normalcy after suffering from cancer, there is a substantial need for support and evaluated programs. METHODS: The study had a quasi-experimental design with an intervention group (IG) and a comparison group (CG). We defined performance-related outcomes (e. g. return to work, self-assessed working capacity), asked patients if they needed further vocational advice and how helpful they estimated the rehabilitation treatment. 1 year after the end of rehabilitation 309 employed patients had completed the study (65%). We addressed our research questions using non-parametric tests, t-tests, analyses of variance and logistic regressions. RESULTS: Of the 309 patients 58% started rehabilitation not later than 14 days after the end of acute treatment while the other 42% had finished their treatments at least some weeks or even months ago. Patients of the IG evaluated the work-related rehabilitation offers significantly better and needed less additional vocational advice after the end of rehabilitation (n. s.). Regarding the patients, who started rehabilitation not later than 14 days after the end of acute treatment (beginning of rehabilitation n=269, 12 months after rehabilitation n=174), the IG achieved a slightly higher return-to-work-rate 12 months after the end of rehabilitation (81% IG, 76% CG, n. s.). Above that the IG estimated their subjective working capacity significantly more often as fully re-established (IG 46%; CG 29%, p=0,030). CONCLUSIONS: A high percentage of the patients return to work (78%). These results show the success of oncological rehabilitation in helping patients to return to work. In addition, the occupation-related rehabilitation program enhances subjective variables as the satisfaction of the patients regarding the information and the improvement of the patients' working-capacity.


Assuntos
Hospitalização/estatística & dados numéricos , Neoplasias/epidemiologia , Neoplasias/reabilitação , Reabilitação Vocacional/métodos , Retorno ao Trabalho/estatística & dados numéricos , Desemprego/estatística & dados numéricos , Avaliação da Capacidade de Trabalho , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Oncologia/estatística & dados numéricos , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde/métodos , Prevalência , Prognóstico , Avaliação de Programas e Projetos de Saúde , Reabilitação Vocacional/estatística & dados numéricos , Fatores de Risco , Resultado do Tratamento
2.
Nano Lett ; 11(12): 5309-15, 2011 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-22029286

RESUMO

A novel approach for the fabrication of transistors and circuits based on individual single-crystalline ZnO nanowires synthesized by a low-temperature hydrothermal method is reported. The gate dielectric of these transistors is a self-assembled monolayer that has a thickness of 2 nm and efficiently isolates the ZnO nanowire from the top-gate electrodes. Inverters fabricated on a single ZnO nanowire operate with frequencies up to 1 MHz. Compared with metal-semiconductor field-effect transistors, in which the isolation of the gate electrode from the carrier channel relies solely on the depletion layer in the semiconductor, the self-assembled monolayer dielectric leads to a reduction of the gate current by more than 3 orders of magnitude.

3.
Rehabilitation (Stuttg) ; 51(1): 31-8, 2012 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-21976297

RESUMO

AIMS: Returning to work after cancer frequently plays an important role for patients of working age. Accordingly, occupation and return to work are key issues for these patients during rehabilitation. So far there is only little empirical evidence from Germany concerning the expectations cancer patients in inpatient rehabilitation hold in relation to their return to work. Negative expectations may hamper returning to work. The context of rehabilitation offers the opportunity to work on potential problems to prepare a successful re-entry into employment. The aim of this study is to analyze the expectations of patients towards getting back to work and how helpful in this respect they estimate the work-related therapies provided during rehabilitation. Furthermore we asked whether professional support should be offered already before getting into inpatient rehabilitation and to what extent they have experienced that kind of help. METHODS: We conducted semi-structured qualitative interviews with 32 cancer patients who participated in inpatient cancer rehabilitation. All patients had been recruited within the same clinic. Interviews were analyzed based on Mayring's "Qualitative Content Analysis". RESULTS: The majority of the patients experienced positive reactions from their occupational environment after learning about the diagnosis. Most of them are optimistic to get help from colleagues and supervisors when returning to work. Prior to their rehabilitation stay 47% had received counseling on cancer and return to work from general practitioners or oncologists. Regarding the occupation-related offers during rehabilitation, the results suggest that women and men have different needs. Women consider them to be more helpful than men. CONCLUSIONS: The results indicate that after having received their diagnosis most cancer patients do not experience negative reactions from their work environment and consequently report few worries with regard to returning to work. The different views on work-related offers during rehabilitation indicate that the concepts of occupation-related therapies within cancer rehabilitation might be optimized by taking the different needs of male and female patients into account.


Assuntos
Emprego/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Indústrias/estatística & dados numéricos , Neoplasias/epidemiologia , Neoplasias/reabilitação , Adulto , Idoso , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência
4.
Artigo em Alemão | MEDLINE | ID: mdl-22441522

RESUMO

Due to improved prognosis most cancer survivors are nowadays able to return to work. This review explored gender-related differences in work-related outcomes after cancer. A systematic search of studies on work-related issues in cancer survivors published between January 2001 and July 2011 was conducted. 44 original publications met the inclusion criteria (adult cancer survivors, focus on work-related outcomes, gender-specific report of results). The results of these studies indicate that impaired work ability is more common among female cancer survivors than among male cancer survivors as well as the reduction of working hours and income losses. Supportive work environments seem to be particularly helpful for the successful and long-lasting re-integration of female survivors. More systematic research and separate analyses for women and men are needed to fully comprehend gender differences in work-related outcomes. Broader knowledge can then be helpful in creating gender-specific return-to-work interventions.


Assuntos
Doença Crônica/epidemiologia , Doença Crônica/reabilitação , Emprego/estatística & dados numéricos , Neoplasias/epidemiologia , Neoplasias/reabilitação , Sobreviventes/estatística & dados numéricos , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Distribuição por Sexo
5.
Phys Rev Lett ; 103(15): 152002, 2009 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-19905623

RESUMO

Azimuthal single-spin asymmetries of leptoproduced pions and charged kaons were measured on a transversely polarized hydrogen target. Evidence for a naive-T-odd, transverse-momentum-dependent parton distribution function is deduced from nonvanishing Sivers effects for pi(+), pi(0), and K(+/-), as well as in the difference of the pi(+) and pi(-) cross sections.

6.
Australas Phys Eng Sci Med ; 29(1): 1-12, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16623216

RESUMO

In this paper an algorithm for calculating 3-D dose distributions within the brain is introduced and adapted to the demands of modem radiosurgery. The dose calculation with this model is based on a 3-D distribution of the primary photon intensity which is calculated with a ray casting algorithm. A prelocated matrix takes into account field sizes as well as modifying elements as collimator positions (MLC), blocks, wedges and compensators. Monte Carlo precalculated monoenergetic kernels from 0.1 MeV to 50 MeV were at our disposal. The components of the spectrum were either determined by deconvoluting depth dose curves measured in water or analyzed with a Ge-Li detector system in the case of 60Co. The calculated fluence distribution has to be superposed to the complete kernel containing the spatial energy deposition. Inhomogeneities and tissue interface phenomena (rhoe, Z) have been investigated. The divergence of the rays and the curved surface of the patient are taken into account. Assuming homogenous media, it is possible to shorten the computation time by using the Fast Fourier Transformation (FFT) delivering a first overview within seconds. The algorithm was evaluated and verified under specific conditions of small fields as used in radiosurgery and compared to dose measurements and Monte Carlo calculations. In using both the fast algorithm (FFT) for mainly homogenous conditions on one hand and the very precise superposition for inhomogeneous cases on the other, this algorithm can be a very helpful instrument especially for critical locations in the skull.


Assuntos
Algoritmos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/radioterapia , Imageamento Tridimensional/métodos , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Radiocirurgia/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Neoplasias Encefálicas/fisiopatologia , Simulação por Computador , Humanos , Modelos Biológicos , Radiometria/métodos , Dosagem Radioterapêutica , Eficiência Biológica Relativa , Reprodutibilidade dos Testes , Espalhamento de Radiação , Sensibilidade e Especificidade , Crânio/diagnóstico por imagem , Crânio/fisiopatologia , Técnica de Subtração
7.
Australas Phys Eng Sci Med ; 28(4): 223-31, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16506619

RESUMO

Because of the ongoing development to more complex non-coplanar techniques in radiotherapy, the use of modem computer graphics while designing a dose plan becomes increasingly essential and more important. In this paper, we describe a concept to simulate 3D conformal treatment techniques on the computer. All important components of the treatment device and relevant patient structures are mapped to an internal model, which allows simulation of motion sequences as well as the interactive adjustment of treatment parameters. The intention of this user interface is to save time by using mainly graphical modules in the optimization process instead of running through the dose calculation every time.


Assuntos
Gráficos por Computador , Imageamento Tridimensional/métodos , Radiometria/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Assistida por Computador/métodos , Software , Interface Usuário-Computador , Algoritmos , Simulação por Computador , Humanos , Modelos Biológicos , Dosagem Radioterapêutica , Design de Software
8.
Int J Radiat Oncol Biol Phys ; 41(2): 459-63, 1998 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-9607365

RESUMO

PURPOSE: The use of positioning and immobilization techniques during external beam irradiation of the female breast is time consuming and expensive. The currently available standardized positioning devices are insufficient. For this reason, we designed a new and generally useable hard foam positioning support cushion for the use during breast irradiation, and tested its clinical usefulness in a prospective study. METHODS AND MATERIALS: Fifty-five female breast cancer patients receiving adjuvant radiotherapy following breast-conservative surgery were irradiated either without immobilization (n = 27) or with the positioning support cushion (n = 28). The time necessary for patient setup, the lying subjective comfort and--comparing portal images with simulator images--the reproducibility of the set up were determined. RESULTS: Irradiation reproducibility was significantly improved (average deviation without positioning support cushion: 8.4 mm, with positioning support cushion: 6.1 mm, p < 0.001). The time required for the positioning of the patient with positioning support cushion was in average 73 s, without cushion it was 55 s. A significantly higher proportion of patients (72%) found the position with the positioning support cushion as pleasant, whereas only 46% of patients were pleased with the position without cushion. CONCLUSION: The positioning support cushion designed in our department makes a substantial contribution to quality assurance in breast irradiation. It significantly increases the patients' comfort in a supine position. In contrast to conventional positioning and fixation aids it may be quickly and easily applied at low costs. Therefore, its use can be recommended.


Assuntos
Neoplasias da Mama/radioterapia , Imobilização , Roupas de Cama, Mesa e Banho , Desenho de Equipamento , Feminino , Humanos , Pessoa de Meia-Idade , Satisfação do Paciente , Estudos Prospectivos , Radioterapia Adjuvante , Reprodutibilidade dos Testes , Decúbito Dorsal
9.
Int J Radiat Oncol Biol Phys ; 29(1): 183-6, 1994 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-8175428

RESUMO

PURPOSE: A high dose rate (HDR) afterloading technique for prevention of vascular stenosis or occlusion after percutaneous transluminal arteriography and subsequent stent implantation caused by intimal hyperplasia is presented. METHODS AND MATERIALS: The frequency of recurrent stenosis or occlusion following implantation of stents into peripheral arteries is relatively high. The cause of relapse is rapid intimal hyperplasia. To prevent proliferation of the intimal layer, intravascular brachytherapy was performed in cases of recurrent vascular occlusion or severe stenosis. After recanalization by percutaneous transluminal angioplasty and stent implantation, a 9-French-ReKa catheter was placed within the lumen of the stent. This catheter served as a guide for a 5-French flexible applicator. Then after individual calculation of the isodose, 12 Gy were applied to the vessel wall. This procedure was followed by 72 h of heparinization. Follow-up by Doppler digital subtraction angiography and magnetic resonance imaging was done 3, 6, and 12 months after the procedure and later on once a year. RESULTS: Intraluminal irradiation was performed in 13 patients (nine male and four female). All patients had a clinically relevant restenosis or reocclusion in the superficial femoral artery (clinical stage according to Fontaine IIb-III). Follow-up time ranged from 3-27 months. After irradiation the stented area remained patent in all cases and there were no signs of recurrent stenosis in the treated arterial segment. CONCLUSION: With high dose rate 192Ir afterloading after percutaneous transluminal angioplasty and subsequent stent implantation restenosis or reocclusion caused by intimal hyperplasia can be prevented.


Assuntos
Arteriopatias Oclusivas/radioterapia , Braquiterapia/métodos , Idoso , Angioplastia com Balão , Arteriopatias Oclusivas/cirurgia , Divisão Celular , Endotélio Vascular/citologia , Feminino , Humanos , Masculino , Stents
10.
Int J Radiat Oncol Biol Phys ; 42(5): 959-67, 1998 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-9869216

RESUMO

PURPOSE: Very young children with medulloblastoma are considered to have a worse prognosis than older children. As radiotherapy remains an important part of the treatment, the adverse prognosis could be due to inadequate radiation treatment rather than biological factors. We analyzed the published literature to examine the impact of radiotherapy on survival in this group. METHODS AND MATERIALS: A Medline search was performed and we reviewed studies of treatment of medulloblastoma where radiotherapy was delivered using megavoltage equipment and the minimum follow-up allowed the calculation of 5-year survival rates. RESULTS: Thirty-nine studies were published between 1979 and 1996 with a treatment including craniospinal irradiation and boost to the posterior fossa. Eleven studies comprising 1366 patients analyzed survival by age at diagnosis. Eight of 11 studies showed a worse 5-year survival for the younger patient group which reached statistical significance in two. There is also a suggestion of a higher proportion of children with metastatic disease at presentation in the very young age group. The usual policy in younger children was to give a lower dose of radiotherapy to the craniospinal axis (CSA) and posterior fossa (PF) with reduction of dose in the range of 15 to 25% compared to standard treatment. As dose reduction to the posterior fossa is associated with worse survival and local recurrence is the predominant site of failure, the major determinant of worse survival in very young children with medulloblastoma may be suboptimal radiotherapy. Protocols including postoperative chemotherapy with delayed, omitted, or only local tumor irradiation do not reach survival rates of protocols with standard radiotherapy, also suggesting a continued importance for irradiation. CONCLUSION: Very young children with medulloblastoma have a worse prognosis than older children. Inadequate radiation dose and technique to the primary tumor region may be a major contributing factor. Current chemotherapeutic regimes alone are not sufficient to compensate for reduced radiation doses and volumes.


Assuntos
Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/radioterapia , Meduloblastoma/mortalidade , Meduloblastoma/radioterapia , Tumores Neuroectodérmicos Primitivos/mortalidade , Tumores Neuroectodérmicos Primitivos/radioterapia , Fatores Etários , Neoplasias Encefálicas/patologia , Pré-Escolar , Fossa Craniana Posterior , Humanos , Lactente , Meduloblastoma/patologia , Estadiamento de Neoplasias , Tumores Neuroectodérmicos Primitivos/patologia , Prognóstico , Análise de Sobrevida
11.
Int J Radiat Oncol Biol Phys ; 51(5): 1328-35, 2001 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-11728694

RESUMO

PURPOSE: To confirm our assumptions regarding factors that apparently cause psychological distress related to adjuvant radiotherapy in breast cancer patients and to evaluate variables that can predict therapy-associated distress. METHODS AND MATERIALS: Between January 1997 and April 1998, 111 women (33-84 years) with early-stage breast cancer were irradiated (56 Gy) after breast-conserving surgery. Patients were given self-assessment questionnaires on the first and last day of radiotherapy. Statistical analysis was performed using the structural equation model LISREL, variance analysis, and regression analysis. RESULTS: The internal subject-related factors (coping, radiation-related anxiety, physical distress, psychological distress) reciprocally influenced each other, whereas external radiotherapy-specific factors (environmental influence, confidence in the medical staff) were causally related to coping, anxiety, and distress. Fifty-three percent of the women felt distressed because cancer affected the breast; 48% were initially afraid of radiotherapy. For 36%, anxiety was not reduced during treatment. Highly distressed women were identified by the following parameters: < or =58 years; initial anxiety; they were affected by having breast cancer, were negatively affected by environmental factors, and did not find distraction helpful. CONCLUSION: Despite considerable individual variability in breast cancer patients, it seems possible to identify women who run a high risk of therapy-associated distress. In these patients, psychosocial support is necessary to reduce treatment-related anxiety and to stabilize confidence in the medical staff.


Assuntos
Neoplasias da Mama/radioterapia , Radioterapia/psicologia , Estresse Psicológico/etiologia , Adaptação Psicológica , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/psicologia , Feminino , Humanos , Pessoa de Meia-Idade
12.
Int J Radiat Oncol Biol Phys ; 36(4): 835-40, 1996 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-8960510

RESUMO

PURPOSE: Percutaneous transluminal angioplasty (PTA) with or without stent implantation is the accepted standard in the therapy of occlusive arterial disease. Despite improvements in the technique and medical equipment, there is still a restenosis rate of up to 40%. A high-dose-rate afterloading technique to avoid vascular stenosis or occlusion after PTA and subsequent stent implantation caused by intimal hyperplasia is presented with long-term results. METHODS AND MATERIALS: Intravascular brachytherapy with a 10-Ci 192Ir source was performed in cases of recurrent vascular occlusion or stenosis which appeared within 6 months after a previous PTA. After recanalization by PTA and stent implantation, a 9-Fr ReKa catheter was positioned within the stent to center the applicator with its tip 2 cm below the stent. This catheter served as a guide for a 5-Fr flexible applicator. After this procedure the isodose was calculated and a 12-Gy to 3-mm source distance was applied. The procedure was followed by 72 h of heparinization. RESULTS: From May 1990 to June 1996, 28 patients (21 male and seven female) were treated with endovascular brachytherapy. All patients had a clinically relevant restenosis or reocclusion of the arteria femoralis. Follow-up time ranged from 1 to 71 months. Twenty-eight patients had a sufficient follow-up time; 25 of these patients were examined. Twenty-one patients had treated vessel segments; four patients had no flow in the treated area. Two patients moved away with unknown addresses, and one patient died without any follow-up examination. Radiation-associated side effects were not notable. CONCLUSION: Intraluminal brachytherapy with 192Ir is a safe and useful procedure to avoid endovascular hyperplasia after transluminal percutaneous angioplasty.


Assuntos
Angioplastia com Balão , Arteriopatias Oclusivas/radioterapia , Artéria Femoral/efeitos da radiação , Radioisótopos de Irídio/uso terapêutico , Stents , Idoso , Idoso de 80 Anos ou mais , Arteriopatias Oclusivas/prevenção & controle , Arteriopatias Oclusivas/terapia , Terapia Combinada , Feminino , Artéria Femoral/patologia , Seguimentos , Humanos , Hiperplasia/prevenção & controle , Masculino , Pessoa de Meia-Idade , Doenças Vasculares Periféricas/prevenção & controle , Doenças Vasculares Periféricas/radioterapia , Doenças Vasculares Periféricas/terapia , Dosagem Radioterapêutica , Recidiva , Túnica Íntima/patologia , Túnica Íntima/efeitos da radiação
13.
J Med Chem ; 35(22): 4020-6, 1992 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-1359142

RESUMO

The synthesis and dopaminergic properties of a novel type of dopamine agonist is described. The number and kind of essential structural elements differ significantly from that of the rigid apomorphine-type dopamine agonists. Using standard molecular modeling techniques, a conformational model is developed proposing a U-shaped conformation which might be energetically preferred through aromatic pi-pi-interactions between both of the electron rich aromatic structural elements of this class of compounds. Superimposition of conformations of the lead compound 28 with apomorphine yields a novel model explaining the atypical structure-activity relationships found in this class of indolealkylamines.


Assuntos
Dopaminérgicos/síntese química , Indóis/síntese química , Animais , Ligação Competitiva , Corpo Estriado/metabolismo , Dopaminérgicos/metabolismo , Dopaminérgicos/farmacologia , Técnicas In Vitro , Indóis/metabolismo , Indóis/farmacologia , Masculino , Modelos Moleculares , Conformação Molecular , Ratos , Ratos Wistar , Receptores de Dopamina D2/metabolismo , Comportamento Estereotipado/efeitos dos fármacos , Relação Estrutura-Atividade
14.
J Med Chem ; 42(12): 2235-44, 1999 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-10377229

RESUMO

A series of 2- or 8-trifluoromethylsulfonyloxy (TfO) and 2- or 8-methylsulfonyloxy (MsO) 11-piperazinyldibenzodiazepines, -oxazepines, and -thiazepines were synthesized and evaluated in pharmacological models for their potential clozapine-like properties. In receptor binding assays, the 2-TfO analogues (18a, GMC2-83; 24, GMC3-06; and previously reported GMC1-169, 9a) of the dibenzazepines have profiles comparable to that of clozapine, acting on a variety of CNS receptors except they lack M1 receptor affinity. Introduction of 2-TfO to clozapine leads to compound 9e (GMC61-39) which has a similar binding profile as that of clozapine including having M1 receptor affinity. Interestingly, the MsO analogues, as well as the 8-TfO analogues, have no or weak dopaminergic and serotonergic affinities, but all 8-sulfonyloxy analogues do have M1 affinities. In behavioral studies performed to indicate the potential antipsychotic efficacy and the propensity to induce EPS, 2-TfO analogues blocked effectively the apomorphine-induced climbing in mice in a dose-dependent manner with ED50 values (mg/kg) of 2.1 sc for 9a, 1.3 po for 18a, 2.6 sc for 24, and 8.2 sc for 9e. On the other hand, they showed a clear dose separation with regard to their ED50 values (mg/kg) for indicating catalepsy in rats (>44 sc for 9a, 28 po for 18a, 30 sc for 24, and >50 sc for 9e, respectively), thus implicating a more favorable therapeutic ratio (K/A, ED50 climbing/ED50 catalepsy) in comparison with typical neuroleptics such as haloperidol and isoclozapine. Furthermore, compound 18a was also demonstrated to be an orally potent DA antagonist with an ED50 value of 0.7 mg/kg po in the ex vivo L-DOPA accumulation model. The present study contributes to the SAR of 11-piperazinyldibenzazepines, and the 2-TfO analogues of 11-piperazinyldibenzazepines are promising candidates as clozapine-like atypical antipsychotics with low propensity to induce EPS.


Assuntos
Antipsicóticos/síntese química , Benzazepinas/síntese química , Piperazinas/síntese química , Animais , Antipsicóticos/química , Antipsicóticos/metabolismo , Antipsicóticos/farmacologia , Benzazepinas/química , Benzazepinas/metabolismo , Benzazepinas/farmacologia , Encéfalo/metabolismo , Células CHO , Catalepsia/induzido quimicamente , Cricetinae , Antagonistas de Dopamina/síntese química , Antagonistas de Dopamina/química , Antagonistas de Dopamina/metabolismo , Antagonistas de Dopamina/farmacologia , Humanos , Técnicas In Vitro , Masculino , Camundongos , Estrutura Molecular , Piperazinas/química , Piperazinas/metabolismo , Piperazinas/farmacologia , Ratos , Ratos Wistar , Receptor Muscarínico M1 , Receptores Adrenérgicos alfa/metabolismo , Receptores Dopaminérgicos/efeitos dos fármacos , Receptores Dopaminérgicos/metabolismo , Receptores Histamínicos H1/metabolismo , Receptores Muscarínicos/metabolismo , Receptores de Serotonina/metabolismo , Relação Estrutura-Atividade
15.
J Med Chem ; 43(3): 432-9, 2000 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-10669570

RESUMO

WAY100635 (2), N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohe xanecarboxamide, is a silent serotonin 5-HT(1A) antagonist, which is now widely used to study the 5-HT(1A) receptor both in vivo and in vitro. In this paper, we describe the synthesis and in vitro (5-HT(1A) affinity and pA(2) values at guinea pig ileum strips) and in vivo (hypothermia and ultrasonic vocalization) pharmacology at the serotonin 5-HT(1A) receptor of several closely related analogues of 2. Test compounds 12 and 14, in which the arylpiperazine moiety of 2 has been replaced by an arylaminopiperidine moiety, showed no affinity or antagonistic activity at the 5-HT(1A) receptor. Substitution of the o-methoxy group of 2 by larger fluoroalkoxy or sulfonyloxy substituents did not alter the in vitro or in vivo pharmacology to any great extent; in vivo both the fluoropropyl analogue 5 and the triflate analogue 7 are equipotent to WAY100635 itself. The O-desmethyl analogue 3 proved to be the most potent antagonist at the serotonin 5-HT(1A) postsynaptic receptor sites in this series.


Assuntos
Aminopiridinas/síntese química , Piperazinas/química , Piperazinas/síntese química , Piridinas/química , Receptores de Serotonina/efeitos dos fármacos , Antagonistas da Serotonina/síntese química , 8-Hidroxi-2-(di-n-propilamino)tetralina , Aminopiridinas/química , Aminopiridinas/metabolismo , Aminopiridinas/farmacologia , Animais , Lobo Frontal/metabolismo , Cobaias , Hipotermia/induzido quimicamente , Íleo/efeitos dos fármacos , Íleo/fisiologia , Técnicas In Vitro , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Músculo Liso/fisiologia , Piperazinas/metabolismo , Piperazinas/farmacologia , Ensaio Radioligante , Ratos , Receptores de Serotonina/metabolismo , Receptores 5-HT1 de Serotonina , Antagonistas da Serotonina/química , Antagonistas da Serotonina/metabolismo , Antagonistas da Serotonina/farmacologia , Agonistas do Receptor de Serotonina , Relação Estrutura-Atividade , Ultrassom , Vocalização Animal/efeitos dos fármacos
16.
J Med Chem ; 43(3): 517-25, 2000 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-10669578

RESUMO

A series of new analogues of N-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl] 2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-carboxamide (1; GR127935) as potent and selective 5-HT(1B/1D) antagonists were synthesized and evaluated pharmacologically. Their receptor binding profiles were comparable to that of 1. The 1,3,4-oxadiazole isomer 2 and the 4'-aminocarbonyl and 4'-amidinyl analogues (9 and 10) of 1 had higher affinities at the rat 5-HT(1B) receptor (IC(50) = 0.93, 1. 3, and 0.5 nM, respectively) and calf 5-HT(1D) receptor (IC(50) = 37, 10, and 3 nM, respectively) than did 1 (1.6 and 52 nM for rat 5-HT(1B) and calf 5-HT(1D) receptors, respectively). In the functional in vitro testing of 5-HT(1B/1D) antagonistic properties, 2, 9, 10, 11b (O-demethylated derivative of 2), 13a (O-methylsulfonyl analogue of 2), and 16 (which differs from 2 with a sulfonamide linker) showed more pronounced effects in the K(+)-induced 5-HT release in the cortex of guinea pig than did 1 and 3 (SB224289). Compounds 2, 9, and 10 were equally potent as 1 in rabbit saphenous vein model (pA(2) > 9). A biochemical study of 2 with in vivo microdialysis in the rat brain showed that it is capable of augmenting citalopram (a selective serotonin reuptake inhibitor, SSRI) induced 5-HT release in rat ventral hippocampus, while preventing the decrease in acetylcholine release elicited by citalopram administration. The molecular structure of 2 was determined by single-crystal X-ray analysis. The log P and log D values of these compounds were calculated. This study contributes to the SAR study of N-piperazinylphenyl biphenylcarboxamides as selective and potent 5-HT(1B/1D) antagonists.


Assuntos
Compostos de Bifenilo/síntese química , Piperazinas/síntese química , Receptores de Serotonina/efeitos dos fármacos , Antagonistas da Serotonina/síntese química , Sulfonamidas/síntese química , Acetilcolina/metabolismo , Animais , Compostos de Bifenilo/química , Compostos de Bifenilo/metabolismo , Compostos de Bifenilo/farmacologia , Bovinos , Cristalografia por Raios X , Cobaias , Hipocampo/metabolismo , Técnicas In Vitro , Masculino , Microdiálise , Estrutura Molecular , Contração Muscular/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/fisiologia , Piperazinas/química , Piperazinas/metabolismo , Piperazinas/farmacologia , Coelhos , Ensaio Radioligante , Ratos , Ratos Wistar , Receptor 5-HT1B de Serotonina , Receptor 5-HT1D de Serotonina , Receptores de Serotonina/metabolismo , Veia Safena/efeitos dos fármacos , Veia Safena/fisiologia , Serotonina/metabolismo , Antagonistas da Serotonina/química , Antagonistas da Serotonina/metabolismo , Antagonistas da Serotonina/farmacologia , Relação Estrutura-Atividade , Sulfonamidas/química , Sulfonamidas/metabolismo , Sulfonamidas/farmacologia
17.
J Med Chem ; 43(6): 1149-57, 2000 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-10737747

RESUMO

As part of our research program toward new, potential antidepressants, a series of unsymmetrical ureas has been prepared and evaluated as 5-HT reuptake inhibitors with 5-HT(1B/1D) antagonistic activities. The design of these compounds was based on coupling of various indole derivatives, previously shown to inhibit 5-HT reuptake, to three different aniline moieties, which are part of known 5-HT(1B/1D) ligands. Binding experiments in rat frontal cortex using [(125)I]iodocyanopindolol, in calf striatum using [(3)H]5-HT, and in rat hippocampus using [(3)H]8-OH-DPAT as radioligands, respectively, revealed significantly higher affinity at the 5-HT(1B) receptor as compared to the affinities for the 5-HT(1A) and 5-HT(1D) receptors for a number of compounds, among them 4-(5-fluoro-1H-indol-3-yl)piperidine-1-carboxylic acid [4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]amide (5), the corresponding 4-fluoro-1H-indol-3-yl analogue 21a, and the corresponding 6-fluoro-1H-indol-3-yl analogue 21b. Conformational restriction of the aniline moiety in 5 only slightly enhanced the 5-HT(1B) affinity, whereas introduction of an aniline moiety with higher conformational flexibility resulted in a less potent 5-HT(1B) receptor ligand as compared to 5. The functional 5-HT(1B/1D) antagonistic activity was investigated using the rabbit saphenous vein model as well as the [(3)H]5-HT release from guinea pig cortical slices. All new compounds tested in the rabbit saphenous vein model were shown to antagonize the sumatriptan-evoked contractile responses with pA(2) values ranging from 7.3 to 8.7. These observations were consistent with the results of the cortical slice model, in which the ureas were found to block the sumatriptan-induced inhibition of potassium-evoked [(3)H]5-HT release. The 5-HT reuptake inhibition of the ureas determined in rat brain synaptosomes was found to be either increased or decreased as compared to the uncoupled indole derivatives indicating that the reuptake inhibition shown by the ureas is not only due to the indole part but also affected by the aniline moiety of the molecule. Among this series of compounds described the ureas 5, 21a, and 21b seem to be the most interesting candidates showing both 5-HT reuptake inhibition and 5-HT(1B/1D) antagonism in vitro. This dual pharmacological profile should in theory lead to a pronounced enhancement in serotonergic neurotransmission and consequently to a more efficient treatment of depression.


Assuntos
Antidepressivos/síntese química , Indóis/síntese química , Receptores de Serotonina/efeitos dos fármacos , Inibidores Seletivos de Recaptação de Serotonina/síntese química , Antagonistas da Serotonina/síntese química , Animais , Antidepressivos/química , Antidepressivos/metabolismo , Antidepressivos/farmacologia , Encéfalo/metabolismo , Encéfalo/ultraestrutura , Corpo Estriado/metabolismo , Lobo Frontal/metabolismo , Cobaias , Hipocampo/metabolismo , Técnicas In Vitro , Indóis/química , Indóis/metabolismo , Indóis/farmacologia , Contração Muscular/efeitos dos fármacos , Contração Muscular/fisiologia , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/fisiologia , Coelhos , Ensaio Radioligante , Ratos , Receptor 5-HT1B de Serotonina , Receptor 5-HT1D de Serotonina , Receptores de Serotonina/metabolismo , Veia Safena/efeitos dos fármacos , Veia Safena/fisiologia , Serotonina/metabolismo , Antagonistas da Serotonina/química , Antagonistas da Serotonina/metabolismo , Antagonistas da Serotonina/farmacologia , Inibidores Seletivos de Recaptação de Serotonina/química , Inibidores Seletivos de Recaptação de Serotonina/metabolismo , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Sinaptossomos/metabolismo
18.
Neuroscience ; 79(3): 887-91, 1997 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9219951

RESUMO

Olfactory receptor neurons undergo a continuous turnover in adult mammals. It is largely unknown how their axons invade the olfactory bulb and induce synaptic re-organization in glomeruli. Here, the cytochemical localization of lysosomal acid phosphatase has been studied in olfactory bulbs of adult rats and mice. The enzyme has been identified by specific substrate, inhibitors and absence in lysosomal acid phosphatase-knockout mice. Lysosomal acid phosphatase is located in primary and secondary lysosomes, which are unevenly distributed in the olfactory nerve layer and among olfactory glomeruli. In consecutive sections of glomeruli, the intensity of lysosomal acid phosphatase immunoreactivity co-varied with that of growth-associated phosphoprotein. Electron microscopically, differential lysosomal acid phosphatase staining in glomeruli corresponded to different proportions of labelled and unlabelled axons. Quantification revealed that lysosomal acid phosphatase labelling was strongest in non-synaptic profiles of terminal axons, while it was weak in or even missing from most synaptic profiles. Hence, growing olfactory axons apparently carry more lysosomal acid phosphatase than those which have established synaptic contacts. Following olfactory deafferentation both lysosomal acid phosphatase activity and growth-associated phosphoprotein-43 are lost from glomeruli, suggesting that both proteins are expressed in olfactory sensory axons during growth, while lysosomal acid phosphatase is apparently not a marker of anterograde terminal degeneration.


Assuntos
Fosfatase Ácida/metabolismo , Axônios/enzimologia , Lisossomos/enzimologia , Glicoproteínas de Membrana/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Receptores Odorantes/fisiologia , Receptores Odorantes/ultraestrutura , Animais , Proteína GAP-43 , Microscopia Eletrônica , Ratos , Ratos Sprague-Dawley
19.
J Nucl Med ; 37(12): 1942-6, 1996 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8970510

RESUMO

UNLABELLED: Previous studies have shown high accuracy for immunoscintigraphy with 99mTc-MAb-174 in patients with squamous-cell carcinoma of the head and neck region compared to CT and MRI. We conducted a prospective study to determine if immunoscintigraphy provides additional diagnostic information for radiation treatment planning. METHODS: Radioimmunoscintigraphy (RIS) was performed on 40 patients (planar, whole-body, SPECT) with histologically confirmed squamous-cell carcinoma (30 primary tumors, 10 recurrences) after injection of the 99mTc (1.1 GBq) labeled monoclonal anti-squamous-cell cancer antibody 174H0.64 (murine IgG1). Results were combined with information obtained by clinical examination, sonography, panendoscopy and x-ray CT. The strategy for radiation treatment and the required treatment volumes were defined with and without immunoscintigraphical findings. RESULTS: Additional diagnostically relevant information from RIS was obtained from 10 patients (25%) with advanced tumors or recurrences. In three patients (7.5%), the treatment volume had to be extended. The therapeutic strategy for seven patients (17.5%) had to be changed due to the detection of metastatic disease beyond the head and neck region. RIS of patients with squamous-cell cancers of the head and neck region with 99mTcMAb-174H0.64 enabled the detection of tumors that were not depicted by other conventional diagnostic imaging procedures. CONCLUSION: The use of RIS in radiation treatment planning of advanced tumors of the head and neck region appears to yield important diagnostic information that may alter patient management.


Assuntos
Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/radioterapia , Radioimunodetecção , Tomografia Computadorizada de Emissão de Fóton Único , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Tecnécio
20.
Radiother Oncol ; 40(2): 181-4, 1996 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8884973

RESUMO

Different wound dressings are used for the supportive treatment of patients with radiation-induced skin lesions. Depending on beam quality and energy, an increase of the dose administered to the skin and thus an aggravated skin reaction is to be expected during percutaneous irradiation. The increase of the skin dose during irradiation with photons (Co60, 6 MV, 42 MV) and electrons (7 MeV, 20 MeV, 42 MeV) was determined using thermoluminescence dosimetry. The use of wound dressings during electron irradiation and during soft irradiation therapy does not significantly increase the dose administered to the skin and does not therefore cause any problems. During irradiation with high energy photons only extremely thin dressings should be used; if there is an aggravated skin reaction, the dressing should be taken off before irradiation commences.


Assuntos
Bandagens , Radiodermite/etiologia , Dosagem Radioterapêutica , Elétrons , Humanos , Fótons
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA