In order to substantiate the concept that cocaine behavioral effects may be influenced by histone modification, rats were trained to self-administer cocaine intravenously (0.75 mg/(kg injection)), and were systemically pretreated with sodium butyrate (NaBu), a potent histone deacetylase inhibitor, before the test session during the maintenance phase. The effect of NaBu on a control reinforcer (sucrose)-induced self-administration was also assessed. NaBu (100–200 mg/kg) was inactive in altering the cocaine (0.75 mg/(kg injection))-maintained responding and at the highest dose (400 mg/kg) it did increase cocaine-induced lever presses during the maintenance phase. On the other hand, sucrose-reinforcing potential was not altered when NaBu was given at the highest dose (400 mg/kg). These findings extend previous observations that changes in histone acetylation are relevant to cocaine-induced behavioral effects. Given that histone acetylase inhibitor enhances cocaine-induced behavioral plasticity, the therapeutic benefits of histone acetyltransferase inhibitors warrant further investigation in the experimental models of cocaine abuse. 相似文献
Summary The anti-inflammatory activity of hamamelis distillate has been evaluated with respect to drug concentration (0.64 mg/2.56 mg hamamelis ketone/100 g) and the effect of the vehicle (O/W emulsion with/without phosphatidylcholine (PC) in an experimental study. The effects were compared with those of chamomile cream, hydrocortisone 1% cream and 4 base preparations. Erythema was induced by UV irradiation and cellophane tape stripping of the horny layer in 24 healthy subjects per test. Skin blanching was quantified by visual scoring and chromametry. Drug effects were compared with one another and with an untreated control area, as well as with any action due to the vehicle.UV-induced erythema at 24 h was suppressed by low dose hamamelis PC-cream and hydrocortisone cream. Hydrocortisone appeared superior to both hamamelis vehicles, hamamelis cream (without PC) and chamomile cream. The latter preparation was also less potent than hamamelis PC-cream. Erythema 4 to 8 h after the stripping of the horny layer was suppressed by hydrocortisone (P0.05). Inflammation was also less pronounced following low dose hamamelis PC-cream and chamomile cream. Hamamelis PC-cream, however, appeared less potent than hydrocortisone. In general, visual scoring was more discriminatory than chromametry.The results have demonstrated an anti-inflammatory activity of hamamelis distillate in a PC-containing vehicle. A fourfold increase of drug concentration, however, did not produce an increase in activity. 相似文献
Rationale: Corticosteroids are elevated in certain neuropsychiatric disorders and this may contribute to the neuropsychological impairments
reported in these disorders. Objective: To examine the effects of hydrocortisone on learning, memory and executive function. Methods: Hydrocortisone 20 mg was administered twice daily for 10 days to normal male volunteers in a randomized, placebo control,
crossover, within-subject design. Learning, memory and executive function were measured using selected subtests from the Cambridge
Neuropsychological Test Automated Battery. Results: Hydrocortisone caused impairments of visuo-spatial memory. These included increased within search errors and impaired use
of strategies on the spatial working memory subtest. In addition, administration of hydrocortisone was associated with more
errors in the paired associate learning subtest, although no effect was found on the Tower of London. Hydrocortisone speeded
response latencies in certain tests (pattern and spatial recognition memory). Conclusion: These results indicate that chronic administration of hydrocortisone leads to deficits in certain tests of cognitive function
sensitive to frontal lobe dysfunction and may contribute to the cognitive impairment reported in certain neuropsychiatric
disorders.
Received: 27 July 1998 / Final version: 9 February 1999 相似文献
Recent reports have demonstrated improvement in the clinical status and hemoglobin levels with use of intravenous arginine butyrate in patients with homozygous β-thalassemia and sickle cell disease.
To allow optimalization of therapy, we conducted pharmacokinetic studies in nine patients, five with sickle cell disease and four with β-thalassemia, treated with continuous intravenous infusion of arginine butyrate.
The disappearance of the drug after discontinuation was characterized by a biphasic elimination with an initial rapid phase followed by a slower phase. Redistribution was noted in five of the patients after 11.2 ± 4.0 min. The short half life was the result of both rapid clearance rate of 93.6 ± 31.9 ml/kg/min and small Vc (0.21 ± 0.26 l/kg) and Vss (0.31 ± 0.37 l/kg).
While preliminary results of the effectiveness of arginine butyrate are encouraging with a rise of γ-globin mRNA and F reticulocytes in some patients, the rapid elimination of this agent will probably limit its current use to administration by continuous infusion. 相似文献
The effect of repeated exposure of cutting oil on 8 guinea pigs' skin was evaluated by visual scoring for erythema and skin water vapour loss (SVL) measurement over a 6-week period. The visual scores (measuring severity of erythema) and SVL values were significantly higher on skin treated with cutting oils (positive control) compared to untreated skin (negative control) throughout the study period. The scores and SVL values returned to near-baseline values when cutting oil application was stopped. In addition, the effect of 2 "after-work" emollient creams on 8 guinea pigs' skin repeatedly treated with a cutting oil was assessed by similar methods. The visual scores and SVL values of guinea pig skin that was repeatedly treated with the cutting oil and moisturized with "after-work" emollient creams, were significantly higher than negative and positive control guinea pig skin. It appeared that the 2 "after-work" emollient creams do not alleviate the irritant effect of the cutting oil on guinea pig skin. They appeared to aggravate the irritant effect of the cutting oil. 相似文献