Диссертация: инструкция по подготовке и защите - [13]

Role of hypothalamic histaminergic neurons in mediation of ACTH and beta-endorphin responses to LPS endotoxin in vivo Knigge U., Kjaer A., Jorgensen H., Gar-barg M., Ross C., Rouleau A., WarbergJ. Department of Medical Physiology, Panum Institute, University of Copenhagen, Denmark Neuroendocrinology. 1994 Sep; 60(3): 243 —51 The involvement of hypothalamic hista-minergic neurons in the mediation of the ACTH and beta-endorphin (beta-END) response to lipopolysaccharide (LPS) endotoxin was investigated in conscious male rats. LPS stimulated the release of ACTH and beta-END dose-dependently and increased the hypothalamic concentration of the histamine (HA) metabolite tele-methylhista-mine significantly and that of HA slightly, indicating an increased turnover of neuronal HA. Pretreatment with the HA synthesis inhibitor alpha-fluoromethyl-histidine administered intracerebroventricularly (i.c.v.) or intrape-ritoneally (i.p.) inhibited the ACTH and beta-END response to LPS about 60 %, whereas i.p. administration of the H3 receptor agonist R(alpha)methylHA, which inhibits HA synthesis and release, decreased the response about 50 %. Pretreatment with the H1 receptor antagonist mepyramine (67 micrograms x 2 i.c.v.) inhibited the hormone response to LPS about 50 %, while pretreatment with equimolar doses of the H2 receptor antagonists cime-tidine (67 micrograms x 2 i.c.v.) or ranitidine (83 micro-grams x 2 i.c.v.) had no effect on the LPS-induced release of ACTH and beta-END. When the H1 receptor antagonists mepyramine and cetirizine were administered i.p. in doses (10 mg/kg) which penetrate the blood-brain barrier the hormone response to LPS was inhibited 50 % and 30 %, respectively. Administered i.p. the H2 receptor antagonists had no effect on the hormone response to LPS. We conclude that hypothalamic histaminergic neurons in rats are involved in the mediation of the ACTH and beta-END response to LPS stimulation via activation of central postsynaptic H1 receptors.

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Eur J Pharmacol. 2002 Sep 13;451(2):149—55 Lack of effects of prolonged treatment with phenobarbital or phenytoin on the expression of P-glycoprotein in various rat brain regions Seegers U, Potschka H, Loscher W Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, Bunteweg 17 Building 218, D-30559 Hannover, Germany P-glycoprotein is an ATP-dependent drug transport protein that is predominantly found in the apical membranes of various epithelial cell types in the body, including the blood luminar membrane of the brain capillary endothelial cellsthat make up the blood-brain barrier. Increased P-glycoprotein expression in the blood-brain barrier has been described in epileptogenic brain tissue of patientswith pharmacoresis-tant epilepsy, suggesting that overexpression of P-glyco-protein may be involved in multidrug resistance of epilepsy. Themechanisms underlying the overexpression of P-glycoprotein in brain tissue of epileptic patients are not clear. Two antiepileptic drugs, phenobarbital and pheny-toin, have been reported to up-regulate P-glycoprotein in cell cultures, so that chronic treatment with antiepileptic drugs may enhance P-glycoprotein expression in the blood-brain barrier. To directly address this possibility, wetreated rats with phenobarbital or phenytoin over 11 days and subsequently determined expression of P-gly-coprotein by immunohistochemistry in endothelium and parenchyma of several brain regions, including regions of the temporal lobe,which is often involved in pharmacoresistant types of epilepsy. Except for amoderate increase in the intensity of P-glycoprotein expression in thepiri-form/parietal cortex and cerebellum of phenobarbital-treated rats, no significant P-glycoprotein increases were seen after prolonged treatment with phenobarbital or phenytoin in any brain region examined. In view of re-centfindings that seizures lead to a transient induction of P-glycoprotein in the brain of rats, it seems reasonable to suggest that the overexpression of P-glycoprotein in brain regions of patients with intractable epilepsy is acon-sequence of uncontrolled seizures rather than of chronic treatment with antiepileptic drugs.

Классик на один год

Один австралиец опубликовал в Nature письмо, в котором делился своим опытом обучения будущих исследователей. Он предлагал ученикам оценить качество нескольких журнальных статей, среди которых была одна из так называемого «списка классиков года». (В «классики» можно попасть, если вашу работу в течение года процитируют в научной печати более 400 раз.) Оценки, данные группой, сводились в рейтинг, и, как Вы уже догадались, «классическая» статья часто оказывалась на одном из последних мест. После этого студенты с неподдельным интересом разбирали причины, приведшие к ошибке, и постепенно вырабатывали у себя важнейшее для исследовательской работы умение – умение отличать по-настоящему важное от рядового и повседневного.