Aims We compared the vasoconstrictor effects of 5-HT with those of the selective 5-HT 1B/1D -receptor agonists sumatriptan and rizatriptan in human isolated cranial (middle meningeal) arteries. In addition selective 5-HT 1B -or 5-HT 1D -receptor antibodies were used in combination with semiquantitative immunohistochemical techniques to compare the levels of expression of these receptors in human middle meningeal and coronary arteries. Methods Middle meningeal and coronary arteries were obtained (with consent) from either neurosurgical patients or donor hearts, respectively. Segments of middle meningeal artery were mounted in organ baths for isometric recording and cumulative concentration-effect curves to 5-HT, rizatriptan and sumatriptan were obtained. Frozen fresh sections of middle meningeal and coronary arteries were subjected to standard immunohistochemical techniques using specific 5-HT 1B -or 5-HT 1D -receptor primary antibodies and a radiolabelled secondary antibody. Data were subjected to analysis of variance (anova) and nonlinear regression analysis.Results 5-HT, rizatriptan and sumatriptan were potent vasoconstrictors in human isolated middle meningeal artery (EC 50 values=32, 90 and 71 nm, respectively). A significantly higher level of 5-HT 1B -receptor immunoreactivity was detected in middle meningeal artery compared with coronary artery (anova, F=7.95, DF= 1,4, P<0.05). Conclusions Rizatriptan and sumatriptan act selectively to cause vasoconstriction in human isolated middle meningeal artery and are 10-fold more potent than in human coronary artery. The higher level of expression of 5-HT 1B -receptors in middle meningeal compared with coronary artery provides a pharmacological basis for the craniovascular selectively of both rizatriptan and sumatriptan.Keywords: 5-HT 1B/1D -receptor agonists, human arteries, vasoconstriction importance since this may lead to coronary adverse events Introduction [12, 13]. It has been reported that 5-HT 1B -receptors mediate vasoconstriction in cranial/cerebral arteries and also in It is generally accepted that migraine headache is accompanied by excessive vasodilation of extracerebral, coronary arteries [4][5][6]. However, sumatriptan acts selectively in cranial arteries compared with coronary arteries since the intracranial blood vessels and that the therapeutic action of 5-HT 1B/1D -receptor agonists such as sumatriptan can result, incidence of cardiac adverse-events related to sumatriptan administration in migraineurs is rare. at least in part, from cranial vasoconstriction [1-3] via activation of vascular 5-HT 1B -receptors [4][5][6][7]. (Note in this Previously we have reported two independent coronary artery studies (using different experimental protocols) where report we follow the recently adopted nomenclature of 5-HT 1B -and 5-HT 1D -receptors, however, these subtypes the maximum contraction evoked by the selective 5-HT 1B/1D -receptor agonist rizatriptan was found to be signifiare also known in the literature as 5-HT 1Db and 5-HT 1Da receptors, respectivel...

Maternal thyroid status influences early brain development and, consequently, cognitive and motor function in humans and rats. The biochemical targets of maternal thyroid hormone (TH) action in fetal brain remain poorly defined. A partially thyroidectomized rat dam model was therefore used to investigate the influence of maternal hypothyroxinemia on the specific activities of cholinergic and monoaminergic neurotransmitter metabolic enzymes in the developing brain.Maternal hypothyroxinemia was associated with reduced monoamine oxidase (MAO) activity in fetal whole brain at 16 and 19 days gestation (dg). A similar trend was observed for choline acetyltransferase (ChAT) activity. In contrast, DOPA decarboxylase (DDC) activity was markedly elevated at 21 dg. Further study of these enzymes at 14 dg showed no differences between normal and experimental progeny -suggesting they become TH sensitive after this age. Tyrosine hydroxylase (TyrH) and acetylcholinesterase (AChE) activities were unaffected prenatally. During postnatal development, the activities of TyrH, MAO, DDC and, to a lesser extent, AChE were increased in a brain region-and age-specific manner in experimental progeny.The prenatal disturbances noted in this study may have wide-ranging consequences since they occur when neurotransmitters have putative neurotropic roles in brain development. Furthermore, the chronic disturbances in enzyme activity observed during postnatal life may affect neurotransmission, thereby contributing to the behavioural dysfunction seen in adult progeny of hypothyroxinemic dams.

The influence of maternal hypothyroxinemia on the expression of the glucose transporters, GLUT1 and GLUT3, in rat fetal brain and placenta was investigated. Fetal growth was retarded in hypothyroxinemic pregnancies, but only before the onset of fetal thyroid hormone synthesis. Placental weights were normal, but placental total protein concentration was reduced at 19 days gestation (dg). Immunoblotting revealed a decreased abundance of GLUT1 in placental microsomes at 16 dg, whereas GLUT3 was increased. Fetal serum glucose levels were reduced at 16 dg. In fetal brain, the concentration of microsomal protein was deficient at 16 dg and the abundance of parenchymal forms of GLUT1 was further depressed, whereas GLUT3 was unaffected. Northern hybridization analysis demonstrated normal GLUT1 mRNA levels in placenta and fetal brain.In conclusion, maternal hypothyroxinemia results in fetal growth retardation and impaired brain development before the onset of fetal thyroid function. Glucose uptake in fetal brain parenchyma may be compromised directly, due to deficient GLUT1 expression in this tissue, and indirectly, as a result of reduced placental GLUT1 expression. Though corrected by the onset of fetal thyroid hormone synthesis, these deficits are present during the critical period of neuroblast proliferation and may contribute to long term changes in brain development and function seen in this model and in the progeny of hypothyroxinemic women.

The 1940s was a contentious decade for US media policy. Activists, policymakers, and communication industries grappled over media's normative foundations and regulatory guidelines. At this time, a reform agenda was taking shape at both the grassroots social movement level and inside elite policy circles. This paper examines the tensions within this nascent media reform movement, many of which are still negotiated among media activists today. By recovering contingency and conflict, this research sheds light on larger paradigmatic shifts. It suggests that despite significant reform activism in the 1940s, a commercial, self-regulated media system emerged largely inoculated against further structural challenges. The failures of this reform movement hold important lessons for contemporary activists.

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