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81.
Fátima Martel M. João Martins Isabel Azevedo 《Naunyn-Schmiedeberg's archives of pharmacology》1996,354(3):305-311
1-Methyl-4-phenylpyridinium (MPP+), the neurotoxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), is efficiently taken up and accumulated by rat hepatocytes. However, the nature of the mechanism(s) involved in the hepatic uptake of MPP+ remains partially unknown. The aim of the present study was to further characterize the hepatic uptake of 3H-MPP+, namely by investigating the interactions of catecholamines (which are also efficiently taken up by rat hepatocytes) with MPP1 transport.The accumulation of 3H-MPP+ in isolated rat hepatocytes occurred through saturable and non-saturable mechanisms. The kinetics of the saturable component of 3H-MPP+ uptake was as follows: Vmax = 181.3 ± 11.1 pmol mg protein–1 min–1 and Km = 47.1 M (27.9, 66.3) (n = 5). The diffusion constant (in ml mg protein–1 min–1) for the non-saturable uptake of 3H-MPP+ was 0.00068 (0.00052, 0.00083) (n = 5). From the analysis of the time course of 3H-MPP+ accumulation at a substrate concentration of 100 nM 3H-MPP+, it was found that the rate constant of inward transport of 3H-MPP+ into hepatocytes (kin) was 15.7 ± 3.8 l mg protein–1 min–1, the rate constant of outward transport of 3H-MPP+ from hepatocytes (kout) was 0.077 ± 0.023 min–1 and the equilibrium accumulation (Amax) of 3H-MPP+ was 20.2 ± 2.0 pmol mg protein–1 (n = 36). Decynium22 (1,1-diethyl-2,2-cyanide; 1 M) significantly reduced kin to 6.1 ± 1.8 l mg protein–1 min–1 (P < 0.05) and the equilibrium accumulation (Amax) of 3H-MPP+ to 9.6 ± 1.3 pmol mg protein–1 (P < 0.005) (n = 36). 3H-MPP+ accumulation (in cells incubated with 200 nM 3H-MPP+) was sensitive to (–)-adrenaline, (–)-isoprenaline, (–)-dopamine, (±)-adrenaline and (–)-noradrenaline. The most potent catecholamine in inhibiting 3H-MPP+ uptake was (–)-adrenaline, with an IC50 of 99 (22, 449) M (n = 6). (–)-Adrenaline competitively inhibited 3H-MPP+ uptake, as it significantly increased the Km value of 3H-MPP+ uptake (to 125.4 M (63.6; 187.1); P < 0.02; n = 3) but did not change the Vmax value. The cyanide-derivatives decynium22 and cyanine863 (1-ethyl-2-([1,4-dimethyl-2-phenyl-6-pyrimidinylidene]methyl)quinolinium), which inhibit uptake2 as well as the apical type of the renal transporter for organic cations, potently inhibited 3H-MPP+ uptake with IC50's of 1.4 (0.4–5.3) (n = 6) and 6.5 (2.6–16) (n = 4) M, respectively. Under conditions of monoamine oxidase (MAO) and catechol-O-methyl transferase (COMT) inhibition with either pargyline (500 M + Ro01-2812) (3,5-dinitropyrocatechol; 2 M) or pargyline (500 M) + U-0521(3,4-dihidroxy-2-methyl-propiophenone; l2 M)), (–)-adrenaline (up to 1 mM) had no inhibitory effect on the uptake of 3H-MPP+. Moreover, the uptake of 3H-MPP+ in the presence of pargyline + Ro 01-2812 was significantly lower (66.9 ± 30.4%; P < 0.05; n = 4) than in the absence of these compounds. Therefore, the effect of these MAO and COMT inhibitors on 3H-MPP+ uptake was examined. Interestingly enough, pargyline, Ro 01-2812 and U-0521 were found to inhibit the uptake of 3H-MPP+ (in cells incubated with 200 nM 3H-MPP+): 500 M pargyline, 2 M Ro 012812 and 100 M U-0521 decreased the accumulation of 3H-MPP+ to 38.1 ± 6.8 (n = 5), 60.5 ± 10.1(n = 7) and 71.3 ± 14.5 (n = 7) % of control, respectively.It is concluded that 3H-MPP+ is efficiently taken up by rat hepatocytes by a carrier-mediated mechanism sensitive to catecholamines, decynium22 and cy anine863, and to the enzyme inhibitors pargyline, Ro 01-2812 and U-0521. 相似文献
82.
83.
Câmara Vd Filhote MI Lima MI Alheira FV Martins MS Dantas TO Luiz RR 《Cadernos de saúde pública / Ministério da Saúde, Funda??o Oswaldo Cruz, Escola Nacional de Saúde Pública》1996,12(2):149-158
The main objective of this study was to promote the evaluation of an educational method to identify health risks among adolescents exposed to mercury by their work in gold mining production.The project was carried out with adolescents from a public school from the District of Monsenhor Horta, Municipality of Mariana, state of Minas Gerais. Statistical evaluation of the results revealed a significant increase in the amount of correct answers between the first and fifth stage concerning the definition of work accidents and its importance in relation to work-related diseases, accidents on route to and from the work place and violence at work site itself. 相似文献
84.
João Luis Callegari Lopes Izabel Cristina Casanova Myrian C. Garcia de Figueireido Francisco Carlos Nather Wagner E. Paiva Avelar 《Archives of environmental contamination and toxicology》1992,23(3):351-354
The mussel Anodontites trapesialis (Lam, 1819) was used as an indicator of organochlorine pollutants in the Pardo River, located in the municipality of Ribeirão Preto (21° 07S and 47° 45W), State of São Paulo, Brazil.Biological monitoring was performed for one year at the site of a sugar cane grove on the left bank of the river. Forty-three animals were placed in two aluminum enclosures on the river bottom at this site and 4 animals of each enclosure were sacrificed for pesticide analysis at 3-month intervals, each collection corresponding to one season of the year.The animals were found to have been exposed to DDT, lindane, heptachlor, aldrin and dieldrin. Endrin was not detected in any of the analyses.Research supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP). 相似文献
85.
Stephen R. Blum Ph.D. Saul Feldman D.P.A. Karen Heller M.A. 《Administration and policy in mental health》1991,18(4):257-269
This paper reports findings of a needs assessment in the area of training programs for senior mental health administrators. Questionnaires (N=530) were sent; 169 to county and regional state mental health administrators; 331 went to community mental health administrators. The response rate was 43%. Thirty-four percent of the public sector respondents listed general administration as their first topic; fiscal issues were listed by 19%; 18% listed personnel administration first. Second topics chosen for training by the public sector administrators were general administration (17%), financial management (24%), and personnel (20%). As their first topics of choice for future training, 37% of the community mental health administrators selected general administration areas, 27% selected financial management, and 10% personnel. Training for mental health administrators has the potential for substantial enrichment through the design and implementation of carefully planned programs. Results from this needs assessment show the continued strong need for such training. 相似文献
86.
A term parturient with documented platelet dysfunction presented to the case room for induction of labour. Since this bleeding
abnormality contraindicated the use of lumbar epidural analgesia (LEA), we elected to use an iv fentanyl patientcontrolled
analgesia (PCA) technique for pain relief during labour. The patient received a 50 μg fentanyl loading dose after which 20
μg boluses of fentanyl were self-administered every three minutes as required. The patient received a total of 400 μg of fentanyl
over the 3 1/2 hr of active labour. Mother and neonate tolerated the fentanyl without sequelae. If facilities to monitor the
neonate and mother are present, this method of analgesia is useful in those patients where LEA is contraindicated.
Au terme d’une grossesse, une patiente porteuse d’une dysfonction plaquettaire devait avoir une induction de travail au bloc
obstétrical. Ecartant l’usage d’une epidurale à cause des risques de saignement, nous avons employé du fentanyl en autoanalgésie
(PCA) pour soulager les douleurs du travail. Après une dose initiate de50 μg, la patiente s’injectait des doses de 20 μg de
fentanyl iv aux 3 minutes prn. Elle utilisa un total de 400 μg de fentanyl au cours des 3,5 heures que dura le travail. La
mère et le nouveau-né tolérèrent fort bien ce mode d’analgésie. L’autoanalgésie offre done une alternative au bloc épidural
lorsque ce dernier est contre-indiqué toutefois, nous recommandons de monitorer la mére et le nouveau-né pendant quelques
heures. 相似文献
87.
Bradykinin potentiating and sensitizing activities of new synthetic analogues of snake venom peptides 总被引:3,自引:0,他引:3
The structural requirements for prolonged residual ("sensitizing") activity in bradykinin-potentiating peptides (BPP's) were investigated through a study of seven synthetic BPP's including three not previously described: [Lys6]-BPP9a, [Gly6]potentiator B, and [Lys6,Gln8]potentiator B. The quantitation of the sensitizing activities in the isolated guinea pig ileum indicated that the structural requirements for bradykinin potentiation and for sensitization were not the same. The most potent sensitizers were potentiator B and [Lys6]-BPP9a. 相似文献
88.
J. D. Martins J. P. Monteiro M. C. Antunes-Madeira A. S. Jurado V. M. C. Madeira 《Toxicology in vitro》2003,17(5-6):595-601
Microorganisms are very powerful tools for the supply of information about the toxic effects of lipophilic compounds, since an impairment of cell growth usually occurs as a result of perturbations related, in most cases, with the partition of toxicants in membranes. The thermophilic eubacterium Bacillus stearothermophilus has been used as a model system to identify - and β-endosulfan interactions with the membrane possibly related with the insecticide toxicity. Two approaches have been pursued: (a) bacterial growth is followed and the effects of endosulfan isomers determined; (b) biophysical studies with the fluorescent fluidity probe 1,6-diphenyl-1,3,5-hexatriene (DPH) were performed to assess the effects of - and β-endosulfan on the organization of the membrane lipid bilayer. The effects on growth were quantitatively evaluated by determination of growth parameters, namely the lag phase, the specific growth rate and the cell density reached by cultures in the stationary phase. Growth inhibition by and β-endosulfan dependent on the concentration is diminished or removed by the addition of 2.5 m
Ca2+ to bacterial cultures. Fluorescence DPH polarization consistently showed opposite effects of Ca2+ and - and β-endosulfan on the physical state of bacterial polar lipid dispersions. 相似文献
89.
Randomized, placebo-controlled study of oregovomab for consolidation of clinical remission in patients with advanced ovarian cancer. 总被引:8,自引:0,他引:8
Jonathan S Berek Peyton T Taylor Alan Gordon Mary J Cunningham Neil Finkler James Orr Saul Rivkin Birgit C Schultes Theresa L Whiteside Christopher F Nicodemus 《Journal of clinical oncology》2004,22(17):3507-3516
PURPOSE: To assess oregovomab as consolidation treatment of advanced ovarian cancer and refine the immunotherapeutic strategy for subsequent study. PATIENTS AND METHODS: Patients with stage III/IV ovarian cancer who had a complete clinical response to primary treatment were randomly assigned to oregovomab or placebo administered at weeks 0, 4, and 8, and every 12 weeks up to 2 years or until recurrence. The primary end-point was time to relapse (TTR). RESULTS: One hundred forty-five patients were treated with oregovomab (n = 73) or placebo (n = 72). For the population overall, median TTR was not different between treatments at 13.3 months for oregovomab and 10.3 months for placebo (P =.71). Immune responses were induced in most actively treated patients. This was associated with prolonged TTR. Quality of life was not adversely impacted by treatment. Adverse events were reported with similar frequency in oregovomab and placebo groups, indicating a benign safety profile. A long-term survival follow-up is ongoing. Cox analysis of relapse data identified significant factors: performance status, CA-125 before third cycle, and baseline CA-125. Further evaluation identified a subpopulation with favorable prognostic indicators designated as the successful front-line therapy (SFLT) population. For the SFLT population, TTR was 24.0 months in the oregovomab group compared with 10.8 months for placebo (unadjusted hazard ratio of 0.543 [95% CI, 0.287 to 1.025]), a hypothesis-generating observation. CONCLUSION: Consolidation therapy with oregovomab did not significantly improve TTR overall. A set of confirmatory phase III studies has been initiated to determine whether the SFLT population derives benefit from oregovomab treatment. 相似文献
90.