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排序方式: 共有158条查询结果,搜索用时 15 毫秒
1.
Pregnant rats were injected with a single dose of methylazoxymethanol (MAM, 25 mg/kg) on gestational day 14, 15, 16, 17, 18 or 19 and offspring were tested for their physical development, reflex development and spontaneous activity. MAM treatment did not affect gestational and litter parameters at any of the time of administration studied. Treatment at gestational day 14 (GD14) had the most severe effect on functional neurodevelopment until weaning: righting reflex at surface, chimney test, horizontal wire test resulted altered. Administration at GD15, 16, 18, 19 did not affect the performance in these tests. Offspring treated at GD17 showed a delayed eye opening and an impaired performance in the horizontal wire test. When tested at 50 days of age on the rotarod, all the treated groups performed worse than controls with the exception of GD19 treated offspring. Administration at GD14 and GD15 resulted in increased spontaneous activity of the offspring at 21 days but not at 60 days of age. Different degrees of microencephaly were observed for all treated groups. The results indicate that alterations of physical and behavioral development induced by MAM treatment are dependent on the time of MAM administration, and specific behavioral tests are able to detect different abnormalities and differentiate among treatment groups. Some alterations observed in MAM rats undergo to adaptive changes during maturation of the CNS. 相似文献
2.
3.
M Cardellini F Claudi V Perlini W Balduini F Cattabeni M Cimino 《Il Farmaco; edizione scientifica》1987,42(4):307-317
Some N-alkyl derivatives of 2-(3-hydroxybenzyl)piperidine and of 2-(3,4-dihydroxybezyl)piperidine were synthesized and evaluated pharmacologically in vitro by competition with [3H]spiperone for binding to a homogenized rat striatal tissue, and for ability to stimulate adenylate cyclase. The N-methyl-2-(3,4-dihydroxybenzyl)piperidine shows a fairly good affinity for the D-2 dopamine receptor. The N-alkyl 2-(3,4-dihydroxybenzyl)piperidines produce a faible stimulation of adenylate cyclase activity. 相似文献
4.
C C Naus M Cimino G R Wood M Di Luca F Cattabeni 《Brain research. Developmental brain research》1992,70(1):39-46
Methylazoxymethanol acetate (MAM) is a mitotic inhibitor that has been used to selectively destroy neuroblasts at specific times during gestation. The administration of MAM results in a dose-dependent microencephaly. Following MAM treatment at 15 days of gestation, we have noted an increase in the level of SS immunoreactivity in the neocortex, as determined by radioimmunoassay. Northern blot analysis for preproSS mRNA revealed an increase in MAM-treated cortex. The cellular distribution of SS has been determined using in situ hybridization and immunocytochemistry. There was a 30% increase in the density of SS-immunoreactive neurons in the cortex of the MAM-treated animals. These data suggest that SS neurons in the cortex are spared following MAM treatment at GD 15. 相似文献
5.
M P Abbracchio G Fogliatto A M Paoletti G E Rovati F Cattabeni 《European journal of pharmacology》1992,227(3):317-324
Agonist-induced desensitization of adenosine A1 and A2 receptors was studied in rat striatum slices maintained in carbo-oxygenated Krebs buffer. Slices were exposed to adenosine analogues (either cyclo-pentyl-adenosine or N-ethyl-carboxamido-adenosine) for selected time periods (15-60 min) and repeatedly washed at the end of agonist exposure. Agonist-induced changes of adenosine receptors were then evaluated in P2 fractions prepared from slices by measuring A1 and A2 receptor-regulated adenylate cyclase. A1 receptors were rapidly desensitized by agonist exposure, as shown by a gradual loss of A1 receptor-mediated inhibition of basal cyclase activity and cAMP formation, which was evident within 15-30 min after addition of the adenosine analogue. Agonist-induced desensitization of A1 receptors was dose- and time-dependent, and seemed quicker in onset with cyclo-pentyl-adenosine, according to the higher A1 selectivity of this receptor agonist, with respect to N-ethyl-carboxamido-adenosine. Binding of the A1-selective agonist [3H]cyclo-hexyl-adenosine was unaffected by the desensitization procedure at any of the exposure periods utilized, suggesting that an uncoupling of A1 receptors from their transduction system is indeed responsible for the loss of functional activity. Loss of A1 receptor function was accompanied by a time-dependent amplification of A2 receptor-mediated stimulation of adenylate cyclase activity, likely due to an 'unmasking' of A2 stimulatory receptor function as a consequence of the desensitization of A1 inhibitory receptors. All these effects could be completely counteracted by the concomitant exposure to an adenosine receptor antagonist, and specifically involved the coupling mechanisms of adenosine receptors with their effector system.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
6.
Carlo Centemeri Chiara Bolego Maria P Abbracchio Flaminio Cattabeni Lina Puglisi Geoffrey Burnstock Simonetta Nicosia 《British journal of pharmacology》1997,121(8):1700-1706
- This study was aimed at characterizing ATP-induced rises in cytosolic free calcium ion, [Ca2+]i, in a population of rat striatal astrocytes loaded with the fluorescent Ca2+ probe Fura2, by means of fluorescence spectrometry.
- ATP triggered a fast and transient elevation of [Ca2+]i in a concentration-dependent manner. The responses of the purine analogues 2-methylthio-ATP (2-meSATP), adenosine-5′-O-(2-thiodiphosphate) (ADPβS), as well as uridine-5′-triphosphate (UTP) resembled that of ATP, while α,β-methylene-ATP (α,β-meATP) and β,γ-methylene-ATP (β,γ-meATP) were totally ineffective.
- Suramin (50 μM) had only a minor effect on the ATP response, whereas pyridoxal phosphate-6-azophenyl-2′,4′-disulphonic acid (PPADS) (5 μM) significantly depressed the maximum response.
- Extracellular Ca2+ did not contribute to the observed [Ca2+]i rise: removing calcium from the extracellular medium (with 1 mM EGTA) or blocking its influx by means of either Ni2+ (1 mM) or Mn2+ (1 mM) did not modify the nucleotide responses.
- Furthermore, after preincubation with 10 μM thapsigargin, the nucleotide-evoked [Ca2+]i increments were completely abolished. In contrast, 10 mM caffeine did not affect the responses, suggesting that thapsigargin-, but not caffeine/ryanodine-sensitive stores are involved.
- Both application of the G-protein blocker guanosine-5′-O-(2-thiodiphosphate) (GDPβS) (1 mM) and preincubation with pertussis toxin (PTx) (350 ng ml−1) partially inhibited the nucleotide-mediated responses. Moreover, the phospholipase C (PLC) inhibitor U-73122, but not its inactive stereoisomer U-73343 (5 μM), significantly reduced the ATP-evoked [Ca2+]i rise.
- In conclusion, our results suggest that, in rat striatal astrocytes, ATP-elicited elevation of [Ca2+]i is due solely to release from intracellular stores and is mediated by a G-protein-linked P2Y receptor, partially sensitive to PTx and coupled to PLC.
7.
O. Cantoni P. Sestili F. Cattabeni C. Geroni M. Grandi F. C. Giuliani 《Journal of cancer research and clinical oncology》1989,115(4):373-378
Summary The effects on cellular DNA and cytotoxicity produced by doxorubicin (Dx) and its epimer 4-epidoxorubicin (4E-Dx) were investigated in cultured HeLa cells. 4E-Dx was 2.3 times more cytotoxic than Dx after 1 h of treatment, but the two anthracyclines were equally cytotoxic on longer-term (24h) drug exposure. The different kinetics of cell lethality were related to pharmacodynamic differences between the two drugs. In fact, cellular uptake and efflux rates of 4E-Dx were faster than those of Dx on 1 h of drug exposure but similar after 24 h of treatment. 4E-Dx caused more protein-concealed strand breaks in DNA (single and double) than did Dx, despite a lower potency for free-radical formation. The degree of strand breakage by 4E-Dx was not a linear function of exposure time and, in fact, the rate of strand-break induction declined continuously with time. In contrast, Dx caused an almost linear increase in DNA single-strand breaks with time during 1 h of drug exposure; this was apparently due to its slower uptake. There was little repair of the DNA single-strand breaks produced by Dx upon postincubation for 5 h in a drug-free medium, whereas DNA lesions caused by 4E-Dx were removed with a t
1/2
of about 1.7h. These findings underline the importance of the cellular pharmacokinetics of anthracyclines in relation to their cytotoxic and DNA-damaging effects.Abbreviations used DX
doxorubicin
- 4E-Dx
4-epidoxorubicin 相似文献
8.
In a 66-year-old patient a relationship between the development of gingival hyperplasia and nifedipine treatment was suggested. The hyperplasia was clinically and histologically similar to the gingival hyperplasia induced by diphenylhydantoin. The nifedipine-induced gingival hyperplasia may be probably caused by alterations in calcium metabolism. The withdrawal of the drug results in a complete remission of the disease. 相似文献
9.
Bruno Zappacosta Silvia Persichilli Flaminio Mormile Angelo Minucci Andrea Russo Bruno Giardina Pasquale De Sole 《Clinica chimica acta; international journal of clinical chemistry》2001,310(2)
Background: Breath condensate can give useful information on volatile compounds produced at alveolar level. Actual concentration of H2O2 in breath condensate is dependent on its production at alveolar level and on the efficacy of the detoxifying systems, catalase, glutathione peroxidase, etc. Methods: In the present paper, a simple chemiluminescent method for the determination of the H2O2 collected in exhaled breath is shown and data of both smokers and nonsmokers volunteers are presented. Results: The chemiluminescent response is linear up to 100 μmol/l H2O2. The analytical sensitivity is about 0.01 μmol/l. Most of the nonsmokers have a H2O2 content lower than 0.05 μmol/l, while smokers have a content ranging from 0.1 to 0.6 μmol/l. 相似文献
10.
Trincavelli ML Tuscano D Marroni M Falleni A Gremigni V Ceruti S Abbracchio MP Jacobson KA Cattabeni F Martini C 《Molecular pharmacology》2002,62(6):1373-1384
A(3) adenosine receptor activation has been previously demonstrated to result in both neuroprotective and neurodegenerative effects, depending upon specific pathophysiological conditions. This dual effect may depend on receptor regulation mechanisms that are able to change receptor availability and/or function. In the present study, we investigated desensitization, internalization, and down-regulation of native A(3) adenosine receptors in human astrocytoma cells after exposure to the agonist 2-chloro-N6-(3-iodobenzyl)-N-methyl-5'-carbamoyladenosine (Cl-IBMECA). Cl-IBMECA induced a concentration-dependent inhibition of adenylyl cyclase activity with an EC(50) value of 2.9 +/- 0.1 nM. The effect was suggested to be mediated by A(3) adenosine receptor subtype by the use of selective adenosine receptor antagonists. Cell treatment with pertussis toxin abolished Cl-IBMECA-mediated inhibition of adenylyl cyclase activity, evidencing an A(3) receptor coupling to inhibitory G protein. Short-term exposure to the agonist Cl-IBMECA (100 nM) caused rapid receptor desensitization, within 15 min. Agonist-induced desensitization was accompanied by receptor internalization: A(3) adenosine receptor internalized with rapid kinetics, within 30 min, after cell exposure to 100 nM Cl-IBMECA. The localization of A(3) adenosine receptors on the plasma membrane and in intracellular compartments was directly revealed by immunogold electron microscopy. After desensitization, the removal of agonist led to the restoration of A(3) adenosine receptor functioning through receptor recycling to the cell surface within 120 min. Prolonged agonist exposure (1-24 h) resulted in a marked down-regulation of A(3) adenosine receptors that reached 21.9 +/- 2.88% of control value after 24 h. After down-regulation, the recovery of receptor functioning was slow (24 h) and associated with the restoration of receptor levels close to control values. In conclusion, our results demonstrated that A(3) receptors, in astrocytoma cells, are regulated after short- and long-term agonist exposure. 相似文献