Neurogenic responses mediated by vanilloid receptor-1 (TRPV1) are blocked by the high affinity antagonist, iodo-resiniferatoxin

(1) Stimulation of the vanilloid receptor-1 (TRPV1) results in the activation of nociceptive and neurogenic inflammatory responses. Poor specificity and potency of TRPV1 antagonists has, however, limited the clarification of the physiological role of TRPV1. (2) Recently, iodo-resiniferatoxin (I-RTX) has been reported to bind as a high affinity antagonist at the native and heterologously expressed rat TRPV1. Here we have studied the ability of I-RTX to block a series of TRPV1 mediated nociceptive and neurogenic inflammatory responses in different species (including transfected human TRPV1). (3) We have demonstrated that I-RTX inhibited capsaicin-induced mobilization of intracellular Ca(2+) in rat trigeminal neurons (IC(50) 0.87 nM) and in HEK293 cells transfected with the human TRPV1 (IC(50) 0.071 nM). (4) Furthermore, I-RTX significantly inhibited both capsaicin-induced CGRP release from slices of rat dorsal spinal cord (IC(50) 0.27 nM) and contraction of isolated guinea-pig and rat urinary bladder (pK(B) of 10.68 and 9.63, respectively), whilst I-RTX failed to alter the response to high KCl or SP. (5) Finally, in vivo I-RTX significantly inhibited acetic acid-induced writhing in mice (ED(50) 0.42 micro mol kg(-1)) and plasma extravasation in mouse urinary bladder (ED(50) 0.41 micro mol kg(-1)). (6) In in vitro and in vivo TRPV1 activated responses I-RTX was approximately 3 log units and approximately 20 times more potent than capsazepine, respectively. This high affinity antagonist, I-RTX, may be an important tool for future studies in pain and neurogenic inflammatory models.

Provenance of chalk tesserae from a Roman town-house in Vine Street, Leicester

Fourth-century a.d. chalk tesserae from Roman Leicester (Ratae Corieltavorum) yield rich microfossil assemblages that identify a biostratigraphical age of Cretaceous Late Cenomanian to Early Turonian. The nearest chalk outcrops to Leicester lie in Hertfordshire, Lincolnshire, Yorkshire and north Norfolk, indicating that the material for the tesserae must have been sourced remotely and transported to Ratae. Superimposing the Roman road network onto a map of the relevant Chalk Group distribution provides a guide to possible sources. A process of evaluation identifies Baldock in Hertfordshire and Bridlington in Yorkshire as the most likely sources for the Leicester tesserae.

The supply and movement of Denarii in Roman Britain

Hoards of denarii are common in Britain and the number which have been recorded in detail means that it is now possible to suggest reasonably accurately what a ‘normal’ hoard of a particular date should look like. That being the case, we can then look for variation around that norm and both investigate and speculate what that variation means. A methodology is developed which suggests periods of faster and less rapid coin circulation which has implications for consideration of monetisation. The model also enables us to view where denarii entered circulation; unsurprisingly the army looms large in this picture. The methodology is directly transferable to other provinces and other periods where there are longlived, relatively stable monetary systems.

The Italian academies 1525-1700: networks of culture, innovation and dissent

The intellectual societies known as Academies played a vital role in the development of culture, and scholarly debate throughout Italy between 1525-1700. They were fundamental in establishing the intellectual networks later defined as the ‘République des Lettres’, and in the dissemination of ideas in early modern Europe, through print, manuscript, oral debate and performance. This volume surveys the social and cultural role of Academies, challenging received ideas and incorporating recent archival findings on individuals, networks and texts. Ranging over Academies in both major and smaller or peripheral centres, these collected studies explore the interrelationships of Academies with other cultural forums. Individual essays examine the fluid nature of academies and their changing relationships to the political authorities; their role in the promotion of literature, the visual arts and theatre; and the diverse membership recorded for many academies, which included scientists, writers, printers, artists, political and religious thinkers, and, unusually, a number of talented women. Contributions by established international scholars together with studies by younger scholars active in this developing field of research map out new perspectives on the dynamic place of the Academies in early modern Italy. The publication results from the research collaboration ‘The Italian Academies 1525-1700: the first intellectual networks of early modern Europe’ funded by the Arts and Humanities Research Council and is edited by the senior investigators.

The Golden Age returns: Virgil's fourth Eclogue in the political panegyric of the Italian courts

E. H. Gombrich and others have analysed the uses made of language and imagery from Virgil's famous fourth Eclogue in panegyrical writing by partisans of the Medici dynasty in Florence. This study examines the appropriation of the theme of the returning Golden Age and related motifs from the fourth Eclogue in other Italian courts during the same period, by supporters of the Visconti and Sforza of Milan, the Gonzaga of Mantua, Leonello d'Este and his successors in Ferrara, and the Bentivoglio of Bologna, among others. The deployment of this Virgilian material in political panegyric is seen to be a central element in the self-definition and self-promotion of dynastic rulers throughout the peninsula.