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排序方式: 共有4586条查询结果,搜索用时 15 毫秒
51.
Borna disease virus-induced hippocampal dentate gyrus damage is associated with spatial learning and memory deficits 总被引:5,自引:0,他引:5
Rubin SA Sylves P Vogel M Pletnikov M Moran TH Schwartz GJ Carbone KM 《Brain research bulletin》1999,48(1):475-30
In neonatally inoculated rats, Borna disease virus (BDV) leads to a persistent infection of the brain in the absence of an inflammatory response and is associated with neuroanatomic, developmental, physiologic, and behavioral abnormalities. One of the most dramatic sites of BDV-associated damage in the neonatal rat brain is the dentate gyrus, a neuroanatomic region believed to play a major role in spatial learning and memory. The absence of a generalized inflammatory response to neonatal BDV infection permits direct effects of viral damage to the dentate gyrus to be examined. In this report, neonatally BDV-infected rats at various stages of dentate gyrus degeneration were evaluated in the Morris water maze, a swimming test that assesses the rats' capacity to navigate by visual cues. Our data demonstrate progressive spatial learning and memory deficits in BDV-infected rats that coincided with a gradual decline in the estimated hippocampal dentate gyrus neuron density. 相似文献
52.
Cultured spinal cord motoneurons from day 15 rat embryos (E15) represent a useful model to study Ca2+ channel diversities and their regulation by neurotrophins. Besides the previously identified L-, N- and P-type channels, E15 rat motoneurons also express high densities of R-type channels. We have previously shown that the P-type channel is nearly absent in 60% of these cells, while the R-type contributes to approximately 35% of the total current. Here, we show that chronic preincubation of cultured rat motoneurons with high concentrations (20-100 ng/mL) of brain-derived neurotrophic factor (BDNF) caused a selective up-regulation of the P- and R-type current density available after blocking N- and L-type channels, with no changes to cell membrane capacitance. N- and L-type channels were either not affected or slightly down-modulated by the neurotrophin. The onset of BDNF up-regulation of P/R-type currents had a half-time of 12 h and reached maximal values of approximately 80%. High concentrations of nerve growth factor (NGF; 50-100 ng/mL) had no effect on P/R currents, while BDNF action was prevented by the kinase inhibitor K252a and by the protein synthesis inhibitor anisomycin. These results suggest that chronic applications of BDNF selectively up-regulates the Ca2+ channel types which are most likely to be involved in the control of neurotransmitter release in mammalian neuromuscular junctions. The signal transduction mechanism is probably mediated by TrkB receptors and involves the synthesis of newly functionally active P- and R-type channels. Our data furnish a rationale for a number of recent observations in other laboratories, in which prolonged applications of neurotrophins were shown to potentiate the presynaptic response in developing synapses. 相似文献
53.
M K Campbell L Honess-Morreale D Farrell E Carbone M Brasure 《Health education research》1999,14(2):257-267
This article describes the development and pilot evaluation of a tailored multimedia program to improve dietary behavior among 378 low-income women enrolled in the Food Stamp program in Durham, North Carolina. After randomization to intervention or control groups, participants completed a baseline survey and were resurveyed 1-3 months post-intervention. Measures included dietary fat intake assessed using a brief food-frequency questionnaire, stage of change, knowledge of low-fat foods, self-efficacy and eating behavior questions. The computer-based intervention consisted of a tailored soap opera and interactive 'info-mercials' that provided individualized feedback about dietary fat intake, knowledge and strategies for lowering fat based on stage of change. At follow-up, intervention group participants had improved significantly in knowledge (P < 0.001), stage of change (P < 0.05) and certain eating behaviors (P < 0.05) compared to the control group. Both study groups had lowered their reported fat intake markedly at follow-up (P < 0.001), but did not differ significantly from each other. A majority of participants rated the program as very helpful and were interested in using a similar program in the future. The findings of this pilot study suggest that computerized tailored self-help health promotion programs may be effective educational interventions for lower income and minority populations. 相似文献
54.
Visentin S Amiel P Fruttero R Boschi D Roussel C Giusta L Carbone E Gasco A 《Journal of medicinal chemistry》1999,42(8):1422-1427
Racemic methyl 1,4-dihydro-2, 6-dimethyl-5-nitro-4-(benzofurazanyl)pyridine-3-carboxylates (+/-)-10 and (+/-)-11 and their benzofuroxanyl analogues (+/-)-12 and (+/-)-13 were prepared using a modified Hantzsch reaction that involved the condensation of nitroacetone with methyl 3-aminocrotonate and the appropriate aldehydes. The racemic mixtures were resolved into the corresponding enantiomers. Whole-cell voltage-clamp studies on L-type Ca2+ channels expressed in a rat insulinoma cell line (RINm5F) showed that all the dextrorotatory antipodes were effective agonists of L-type Ca2+ currents, while the levorotatory ones were weak Ca2+ entry blockers. The (+)-enantiomer of benzofurazan-5'-yl derivative 11 demonstrated unusual activity in that, in addition to producing a potentiation of L-type currents, it interfered with the voltage-dependent gating of L-type channels by producing a net delay of their activation at low voltages. This compound represents an interesting tool to probe L-type Ca2+ channel structure and function. 相似文献
55.
Evaluation of vesico-urethral and sweating function in disorders presenting with parkinsonism 总被引:1,自引:0,他引:1
Milena De Marinis Guido Argenta Domenico Mele Antonio Carbone Giulio Baffigo Alessandro Agnoli 《Clinical autonomic research》1993,3(2):125-130
Investigation of vesico-urethral and sweating function was performed in twelve patients with classical idiopathic Parkinson's disease and ten patients with parkinsonism associated with features suggestive of more extensive involvement of the nervous system, as in the Shy—Drager syndrome. The urodynamic studies revealed detrusor hyperreflexia with reduction of maximal cystometric capacity in only one patient with Parkinson's disease (8%), but in nine patients with parkinsonism associated with other features (90%). Urethral sphincter electromyography did not indicate denervation in any patient of either group. Delayed or incomplete relaxation of the urethral sphincter during micturition was observed in seven patients with Parkinson's disease (58%) and in two patients of the other group (20%). Decreased sweating responses were found in both groups of patients when compared with control subjects. Hypohidrosis was more pronounced in parkinsonism associated with other features than in Parkinson's disease. Differences in sweating between the two sides of the body were observed in both groups of patients. Although there are differences in vesico-urethral and sweating function, they do not precisely differentiate between patients with classical Parkinson's disease and those with parkinsonism associated with features suggestive of more extensive involvement of the nervous system. 相似文献
56.
Howard Bailey Peter Kohler Richard Tuttle Paul P. Carbone John A. Hohneker Neil J. Clendeninn George Wilding 《Investigational new drugs》1992,10(4):279-287
One of a novel series of compounds (AMAPS or arylmethylaminopropanediols), 773U82-HCl has shown significant antitumor activity inin vitro and inin vivo tumor systems, but has less animal CNS toxicity than the lead compound in the same series (crisnatol). This study was designed to evaluate the pharmacokinetics, qualitative and quantitative toxicities of 773U82-HCl and to determine the recommended phase II dose (MTD) of 773U82-HCl given as a short infusion daily for 3 days every 3 weeks. Twenty-nine patients with refractory malignancies received 79 courses over 9 dose levels during this study. Doses ranged from 50 to 1060 mg/m2d×3 days. Due to the possibility of local hemolysis with concentrations > 1.5 mg/ml, drug was administered in solutions containing 1.5 mg/ml. Because large volumes were needed at the higher dose levels, the infusion duration was increased from 2 hours to 4 hours. Mild to moderate nausea, vomiting, fatigue, dizziness and headaches were observed. Myelosuppression was the dose limiting toxicity. The recommended phase II dose and schedule was determined to be 800 mg/m2d×3d every 3 weeks. 773U82-HCl plasma concentration-time data were analyzed using a two-compartment pharmacokinetic model. The t1/2 averaged 6 hours and the total body clearance was 75.9 L/hr/m2. The volume of distribution (Vdss) was large, averaging 470 L/m2.Abbreviations ECG
electrocardiogram
- t1/2
half-life
- Vdss
volume of distribution
- HPLC
highperformance liquid chromatography
- Vdss
steady-state volume of distribution
- AUC
area under the concentration × time curve
- CL
total body clearance
- Cmax
peak plasma level
- Vc
central volume of distribution 相似文献
57.
58.
59.
J. F. Cleary Rhoda Arzoomanian Donna Alberti Chris Feierabend Barry Storer Pauline Witt P. P. Carbone George Wilding 《Cancer chemotherapy and pharmacology》1997,39(4):300-306
Purpose: The activity of 5-fluorouracil (5-FU) against colon cancer is enhanced by leucovorin and the combination of 5-FU and levamisole
has activity in the adjuvant treatment of colonic malignancies. The combination of 5-FU with both leucovorin and levamisole
may provide additional benefit in the treatment of colon cancer. Methods: A phase I study to assess qualitative and quantitative toxicities of this three-drug combination and to determine a dose
for further phase II testing was undertaken. The role of levamisole as an immunomodulator was also assessed. Results: A group of 38 patients with incurable etastatic malignancies received 119 cycles of treatment at eight dose levels. 5-FU
(375 mg/m2 per day) and leucovorin (200 mg/m2 per day) were administered intravenously (days 1–5). Levamisole was administered orally (days 1–3 and 15–17) at doses from
30 to 470 mg/m2 per day. Patients received both 5FU/leucovorin and 5-FU/leucovorin/levamisole in random order for their initial two cycles.
All subsequent treatments were with the three-drug combination. Toxicities included nausea, vomiting, stomatitis, thrombocytopenia
and granulocytopenia. Diarrhea was the dose-limiting toxicity at 470 mg/m2 per day levamisole. The addition of levamisole resulted in more toxicity than 5-FU and leucovorin alone. No clinical responses
were seen with this regimen. The addition of levamisole resulted in more immunomodulation than 5-FU and leucovorin alone as
evidenced by release of neopterin from monocytes. Conclusion: With this schedule and dose of 5-FU and leucovorin, the maximum tolerated dose of levamisole was 354 mg/m2. However, given the lack of response and the absence of dose-dependent immunomodulation, this may not be the appropriate
dose for further phase 11 studies.
Received: 20 October 1995 / Accepted: 16 June 1996 相似文献
60.
Proliferative lesions of oviduct and uterus in CD-1 mice exposed prenatally to tamoxifen 总被引:1,自引:3,他引:1
Tamoxifen (TAM) is widely used as adjuvant breast cancer therapy after
surgery and as a chemopreventive agent in women of child-bearing age.
However, TAM therapy has been shown to result in an increased incidence of
endometrial carcinoma in women. The present study was designed to
investigate the effects of TAM (5 mg/kg and 7.5 mg/kg body wt) given i.g.
to pregnant CD-1 mice (1x/day, days 12 through 18 of gestation) on their
female offspring. Progressive proliferative hyperplasia of the oviduct was
frequently seen in TAM-exposed offspring, reaching 100% incidence by 52
weeks in both treatment groups. These females also developed progressive
proliferative uterine lesions, including moderate/severe cystic endometrial
hyperplasia (34-50%) and polypoid adenomas (27-30%) between 53 and 78
weeks. Deciduomas (15%) occurred at young ages (12 and 24 weeks) while
leiomyomas (14%), a malignant leiomyosarcoma, and ovarian granulosa cell
tumors (14%), were found between 72 and 78 weeks. Our findings thus suggest
a strong association between transplacental TAM and reproductive tract
abnormalities in female CD-1 mice.
相似文献