98 research outputs found
Portrait of David Rowbotham, 1958 [picture] /
Condition: good, framed.; Inscriptions: "The Studio, 225 Brunswick Rd, Valley, Bris. David Rowbotham, author poet & journalist" -- verso; Signed "Sibley '58" -- lower c.; Title from accession record.; File no 204/13/64
Pharmacological characterization of the bifunctional opioid ligand H-Dmt-Tic-Gly-NH-Bzl (UFP-505)
BACKGROUND: While producing good-quality analgesia, μ-opioid (MOP) receptor activation produces a number of side-effects including tolerance. Simultaneous blockade of δ-opioid (DOP) receptors has been shown to reduce tolerance to morphine. Here, we characterize a prototype bifunctional opioid H-Dmt-Tic-Gly-NH-Bzl (UFP-505).
METHODS: We measured receptor binding affinity in Chinese hamster ovary (CHO) cells expressing recombinant human MOP, DOP, k-opioid (KOP), nociceptin/orphanin (NOP) receptors. For activation, we measured the binding of GTPγ(35)S to membranes from CHO(hMOP), CHO(hDOP), rat cerebrocortex, and rat spinal cord. In addition, we assessed 'end organ' responses in the guinea pig ileum and mouse vas deferens.
RESULTS: UFP-505 bound to CHO(hMOP) and CHO(hDOP) with (binding affinity) pK(i) values of 7.79 and 9.82, respectively. There was a weak interaction at KOP and NOP (pK(i) 6.29 and 5.86). At CHO(hMOP), UFP-505 stimulated GTPγ(35)S binding with potency (pEC(50)) of 6.37 and in CHO(hDOP) reversed the effects of a DOP agonist with affinity (pK(b)) of 9.81 (in agreement with pK(i) at DOP). UFP-505 also stimulated GTPγ(35)S binding in rat cerebrocortex and spinal cord with pEC(50) values of 6.11-6.53. In the guinea pig ileum (MOP-rich preparation), UFP-505 inhibited contractility with pEC(50) of 7.50 and in the vas deferens (DOP-rich preparation) reversed the effects of a DOP agonist with an affinity (pA(2)) of 9.15.
CONCLUSIONS: We have shown in a range of preparations and assays that UFP-505 behaves as a potent MOP agonist and DOP antagonist; a MOP/DOP bifunctional opioid. Further studies in dual expression systems and whole animals with this prototype are warranted
Recent advances in the non-pharmacological management of postoperative nausea and vomiting
Sir William Collins and Xavier Herbert
Sir William Collins, publisher and Xavier Herbert, author. Hand written comment about the photograph by Xavier Herbert on verso. [Gift of David Rowbotham
Pharmacological profile of the cyclic nociceptin/orphanin FQ analogues c[Cys(10,14)]N/OFQ(1-14)NH2 and c[Nphe(1),Cys(10,14)]N/OFQ(1-14)NH2
In this study we describe the activity of two
cyclic nociceptin/orphanin FQ (N/OFQ) peptides; c[Cys10,14]N/
OFQ(1–14)NH2 (c[Cys10,14]) and its [Nphe1] derivative
c[Nphe1,Cys10,14]N/OFQ(1–14)NH2 (c[Nphe1,Cys10,14]) in
native rat and mouse and recombinant human N/OFQ receptors
(NOP). Cyclisation may protect the peptide from
metabolic degradation.
In competition binding studies of rat, mouse and human
NOP the following rank order pKi was obtained: N/OFQ(1–
13)NH2(reference agonist)>N/OFQ=c[Cys10,14]>>c[Nphe1Cys10,14].
In GTPγ35S studies of Chinese hamster ovary cells expressing
human NOP (CHOhNOP) c[Cys10,14] (pEC50 8.29)
and N/OFQ(1–13)NH2 (pEC50 8.57) were full agonists
whilst c[Nphe1Cys10,14] alone was inactive. Following 30 min
pre-incubation c[Nphe1Cys10,14] competitively antagonised
the effects of N/OFQ(1–13)NH2 with a pA2 and slope factor
of 6.92 and 1.01 respectively. In cAMP assays c[Cys10,14]
(pEC50 9.29, Emax 102% inhibition of the forskolin stimulated
response), N/OFQ(1–13)NH2 (pEC50 10.16, Emax
103% inhibition) and c[Nphe1Cys10,14] (~80% inhibition
at 10 μM) displayed agonist activity. In the mouse vas
deferens c[Cys10,14] (pEC50 6.82, Emax 89% inhibition of
electrically evoked contractions) and N/OFQ(1–13)NH2
(pEC50 7.47, Emax 93% inhibition) were full agonists whilst
c[Nphe1Cys10,14] alone was inactive. c[Nphe1Cys10,14]
(10 μM) competitively antagonised the effects of N/OFQ(1–
13)NH2 with a pKB of 5.66. In a crude attempt to assess
metabolic stability, c[Cys10,14] was incubated with rat brain
membranes and then the supernatant assayed for remaining
peptide. Following 60 min incubation 64% of the 1 nM
added peptide was metabolised (compared with 54% for
N/OFQ-NH2).
In summary, we report that c[Cys10,14] is a full agonist
with a small reduction in potency but no improvement in
stability whilst c[Nphe1Cys10,14] displays tissue (antagonist
in the vas deferens) and assay (antagonist in the GTPγ35S
assay and agonist in cAMP assay) dependent activity
The socio-cultural milieux of the left in post-war Britain
This thesis examines the relationship between activist subjectivities and the shaping of Britain’s late
sixties extra-parliamentary left cultures. Based on the oral narratives of ninety men and women, it
traces the activist trajectory from child to adulthood to understand the social, psychological, and
cultural processes informing the political and personal transformation of young adults within the
new left cultures that emerged in the wake of Britain’s anti-war movement, the Vietnam Solidarity
Campaign (VSC). To this end the study charts the development of the political and cultural shifts on
the left over the decade from the early 1960s to the early 1970s. It shows how throughout this
period dialogue between inner and outer activist life occurred against a background of ongoing
realignment on the left from a fluid, eclectic cultural network around the VSC to a demarcated post-
VSC left after 1969, that saw increasing divergence between a non-aligned libertarian New Left on
the one hand and a Trotskyist far left milieu on the other.
The study seeks to claim a valid space for Britain’s left activist landscape within the political,
social and cultural framework of ‘1968’ and British post-war historiography. Privileging individual
and collective subjectivities, the thesis examines ways of belonging inside Trotskyist and non-aligned
left milieux by situating the respondents, their radical histories and activist cultures within the
changing post-war fabric. It shows that investigating individual and collective memories provides
deeper understanding of the ‘cognitive maps’ that young men and women created, as they
attempted to situate themselves as radical, global beings as well as local, gendered social citizens.
As micro-studies the individual stories reveal how the experience of social, emotional and
political maturation from child to adult intersected with a specific social and political moment – the
formation of a new and distinctive left culture that came to full fruition only in the aftermath of 1968
with the arrival of Women’s Liberation and the new personal politics. Exploring the social and
psychological impact of post-war childhood and youth, the study engages with the political and
emotional impact of Women’s Liberation on the men and women within the cultural context of the different left milieux.
Overall, the thesis questions how, from the mid-1960s to the early 1970s, the variant
cultures of the milieux penetrated public and private spaces, and shaped early life experiences of
work, political activity, family, and political and personal relations in order to understand how
activism shaped social patterns and psychic being
Caro Dr. Marx Carta de uma feminista socialista
A autora dessa carta imaginária, Annette Devereux, é uma personagem fictícia, bem como seu marido, Victor, tipógrafo Cartista, e M. e Mme.Ducrocq. Todos os outros personagens mencionados, no entanto, são figuras históricas e a informação sobre eles é apresentada, na ordem em que aparecem, no final da carta. O argumento e as demandas feitas, os eventos políticos descritos, as revistas e a Falange Fourierista em Wisconsin são todas baseadas na realidade histórica.Abstract The author of this imaginary letter, Annette Devereux, is a fictional character, along with her husband, Victor, the Chartist typographer and M. e Mme. Ducrocq. However, all the others characters mentioned are historical figures and infomation about them is provided in the order in which they appear at the end of the letter. The arguments and demands presented, the political events described, the journals and the Fourierist Phalanx at Wisconsin are all based on historical reality.Key-words: Feminism, Socialism, Communist Manifest, Phalan
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