Drug release enhancement from silicone intravaginal rings by incorporation of water soluble excipients

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We Never Give Up II

Ten years after the production of the initial 'We Never Give Up' film, this documentary filmis a follow-up film about the experiences of ten survivors of South Africa apartheid and their struggle for reparations. Produced by the Human Rights Media Centre, Cape Town, the film was directed and filmed by Cahal McLaughlin in a collaborative relationship with Khulumani Support Group Western Cape.

Further Information:

This documentary film, produced with the Human Rights Media Centre, Cape Town, and in collaboration with Khulumani Support Group Western Cape, is the ten-year follow up to We Never Give Up (2002), which addressed the issues of reparations as dealt with by the South African government and the Truth and Reconciliation Commission. We Never Give Up II (2012) returns to these themes and to the same participants, asking how life has changed in the interim. The process of collaborative practices acknowledges the importance of sharing ownership/authorship in the storytelling processes as well as in validating traumatic experiences by those who survived major and sustained political violence. Made over a two-year period, involving close consultation with participants, the film offers insights, by those most directly affected, to what might constitute legal, financial, social and psychological reparations. The film has been screened in Cape Town, Bloemfontain, Zanzibar Film Festival, Belfast (Belfast Film Festival), Brighton, Guildford, Galway and London, always accompanied by discussion of the issues raised in Q&As. To emphasise the importance of the film for debates on policy around reparations, a 25 minute edited version was selected to be screened on SABC on ‘Special Assignment’ by SABC on April 29th, 2013 (South Africa’s ‘Freedom Day’), followed by a debate with Department of Justice spokesperson, Dr Khotso De Wee. The chapter 'Maureen Never Gave Up' in Daniels, McLaughlin and Pearce (eds.) 'Truth, Dare or Promise' (2013) Cambridge Scholars Press (ISBN: 1-4438-4959-6, ISBN 13: 978-1-4438-4959-3, Release Date: 2013-09-01), which analyses the production of this film, is offered as part of the portfolio.

Ca(2+) sparks promote myogenic tone in retinal arterioles

Background and Purpose: Ca(2+) imaging reveals subcellular Ca(2+) sparks and global Ca(2+) waves/oscillations in vascular smooth muscle. It is well established that Ca(2+) sparks can relax arteries, but we have previously reported that sparks can summate to generate Ca(2+) waves/oscillations in unpressurized retinal arterioles, leading to constriction. We have extended these studies to test the functional significance of Ca(2+) sparks in the generation of myogenic tone in pressurized arterioles.

Experimental Approach: Isolated retinal arterioles (25-40 μm external diameter) were pressurized to 70 mmHg, leading to active constriction. Ca(2+) signals were imaged from arteriolar smooth muscle in the same vessels using Fluo4 and confocal laser microscopy.

Key Results: Tone development was associated with an increased frequency of Ca(2+) sparks and oscillations. Vasomotion was observed in 40% of arterioles and was associated with synchronization of Ca(2+) oscillations, quantifiable as an increased cross-correlation coefficient. Inhibition of Ca(2+) sparks with ryanodine, tetracaine, cyclopiazonic acid or nimodipine, or following removal of extracellular Ca(2+) , resulted in arteriolar relaxation. Cyclopiazonic acid-induced dilatation was associated with decreased Ca(2+) sparks and oscillations but with a sustained rise in the mean global cytoplasmic [Ca(2+) ] ([Ca(2+) ]c ), as measured using Fura2 and microfluorimetry.

Conclusions and Implications: This study provides direct evidence that Ca(2+) sparks can play an excitatory role in pressurized arterioles, promoting myogenic tone. This contrasts with the generally accepted model in which sparks promote relaxation of vascular smooth muscle. Changes in vessel tone in the presence of cyclopiazonic acid correlated more closely with changes in spark and oscillation frequency than global [Ca(2+) ]c , underlining the importance of frequency-modulated signalling in vascular smooth muscle.

Infection-Responsive Drug Delivery from Urinary Biomaterials Controlled by a Novel Kinetic and Thermodynamic Approach

Purpose. The pH-dependent physicochemical properties of the antimicrobial quinolone, nalidixic acid, were exploited to achieve ‘intelligent’ drug release from a potential urinary catheter coating, poly(2-hydroxyethylmethacrylate) (p(HEMA)), in direct response to the elevated pH which occurs at the onset of catheter infection.
Methods. p(HEMA) hydrogels, and reduced-hydrophilicity copolymers incorporating methyl methacrylate, were loaded with nalidixic acid by a novel, surface particulate localization method, and characterized in terms of pH-dependent drug release and microbiological activity against the common urease-producing urinary pathogen Proteus mirabilis.
Results. The pH-dependent release kinetics of surface-localized nalidixic acid were 50- and 10-fold faster at pH 9, representing the alkaline conditions induced by urease-producing urinary pathogens, compared to release at pH 5 and pH 7 respectively. Furthermore, microbiological activity against P. mirabilis was significantly enhanced after loading surface particulate nalidixic acid in comparison to p(HEMA) hydrogels conventionally loaded with dispersed drug. The more hydrophobic methyl methacrylate-containing copolymers also demonstrated this pH responsive behavior, but additionally exhibited a sustained period of zero-order release.
Conclusions. The paradigm presented here provides a system with latent, immediate infection-responsive drug release followed by prolonged zero-order antimicrobial delivery, and represents an ‘intelligent’, infection-responsive, self-sterilizing biomaterial.

Effects of aspirin plus extended-release dipyridamole versus clopidogrel and telmisartan on disability and cognitive function after recurrent stroke in patients with ischaemic stroke in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial:a double-blind, active and placebo-controlled study

The treatment of ischaemic stroke with neuroprotective drugs has been unsuccessful, and whether these compounds can be used to reduce disability after recurrent stroke is unknown. The putative neuroprotective effects of antiplatelet compounds and the angiotensin II receptor antagonist telmisartan were investigated in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial.

Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke

Recurrent stroke is a frequent, disabling event after ischemic stroke. This study compared the efficacy and safety of two antiplatelet regimens--aspirin plus extended-release dipyridamole (ASA-ERDP) versus clopidogrel.