Hemi-orolingual angioedema and ACE inhibition after alteplase treatment of stroke

One hundred seventy-six consecutive patients treated with IV tissue plasminogen activator (tPA) for acute ischemic stroke were examined prospectively, and orolingual angioedema was found in nine (5.1%; 95% CI 2.3 to 9.5). The reaction was typically mild, transient, and contralateral to the ischemic hemisphere. Risk of angioedema was associated with angiotensin-converting enzyme inhibitors (relative risk [RR] 13.6; 95% CI 3.0 to 62.7) and signs on initial CT of ischemia in the insular and frontal cortex (RR 9.1; 95% CI 1.4 to 30.0).

Angiotensin II receptor blockade: is there truly a benefit of adding an ACE inhibitor?

We assessed the blockade of the renin-angiotensin system (RAS) achieved with 2 angiotensin (Ang) antagonists given either alone at different doses or with an ACE inhibitor. First, 20 normotensive subjects were randomly assigned to 100 mg OD losartan (LOS) or 80 mg OD telmisartan (TEL) for 1 week; during another week, the same doses of LOS and TEL were combined with 20 mg OD lisinopril. Then, 10 subjects were randomly assigned to 200 mg OD LOS and 160 mg OD TEL for 1 week and 100 mg BID LOS and 80 mg BID TEL during the second week. Blockade of the RAS was evaluated with the inhibition of the pressor effect of exogenous Ang I, an ex vivo receptor assay, and the changes in plasma Ang II. Trough blood pressure response to Ang I was blocked by 35+/-16% (mean+/-SD) with 100 mg OD LOS and by 36+/-13% with 80 mg OD TEL. When combined with lisinopril, blockade was 76+/-7% with LOS and 79+/-9% with TEL. With 200 mg OD LOS, trough blockade was 54+/-14%, but with 100 mg BID it increased to 77+/-8% (P<0.01). Telmisartan (160 mg OD and 80 mg BID) produced a comparable effect. Thus, at their maximal recommended doses, neither LOS nor TEL blocks the RAS for 24 hours; hence, the addition of an ACE inhibitor provides an additional blockade. A 24-hour blockade can be achieved with an angiotensin antagonist alone, provided higher doses or a BID regimen is used.

Pregnancy outcome following exposure to angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists: a systematic review

The objective was to analyze the outcome following prenatal exposure to angiotensin-converting enzyme inhibitors (ACE-Is) or angiotensin receptor antagonists (ARBs). For this purpose, a systematic review of published case reports and case series dealing with intrauterine exposure to ACE-Is or to ARBs using Medline as the source of data was performed. The publications retained for analysis included patients who were described individually, revealing, at minimum, the gestational age, substance used, period of medication intake, and the outcome. In total, 72 reports were included; 37 articles (118 well-documented cases) described the prenatal exposure to ACE-Is; and 35 articles (68 cases) described the prenatal exposure to ARBs. Overall, 52% of the newborns exposed to ACE-Is and 13% of the newborns exposed to ARBs did not exhibit any complications (P<0.0001). Neonatal complications were more frequent following exposure to ARBs and included renal failure, oligohydramnios, death, arterial hypotension, intrauterine growth retardation, respiratory distress syndrome, pulmonary hypoplasia, hypocalvaria, limb defects, persistent patent ductus arteriosus, or cerebral complications. The long-term outcome is described as positive in only 50% of the exposed children. Fetopathy caused by exposure to ACE-Is or ARBs has relevant neonatal and long-term complications. The outcome is poorer following exposure to ARBs. We propose the term "fetal renin-angiotensin system blockade syndrome" to describe the related clinical findings. Thirty years after the first description of ACE-I fetopathy, relevant complications are, at present, regularly described, indicating that the awareness of the deleterious effect of prenatal exposure to drugs inhibiting the renin-angiotensin system should be improved.

The PG500 series : novel heparan sulfate mimetics as potent angiogenesis and heparanase inhibitors for cancer therapy

Heparan sulfate mimetics, which we have called the PG500 series, have been developed to target the inhibition of both angiogenesis and heparanase activity. This series extends the technology underpinning PI-88, a mixture of highly sulfated oligosaccharides which reached Phase III clinical development for hepatocellular carcinoma. Advances in the chemistry of the PG500 series provide numerous advantages over PI-88. These new compounds are fully sulfated, single entity oligosaccharides attached to a lipophilic moiety, which have been optimized for drug development. The rational design of these compounds has led to vast improvements in potency compared to PI-88, based on in vitro angiogenesis assays and in vivo tumor models. Based on these and other data, PG545 has been selected as the lead clinical candidate for oncology and is currently undergoing formal preclinical development as a novel treatment for advanced cancer.

ACE's role in developing Australia's human capital : a structural analysis

This project explored ways in which Adult and Community Education (ACE) could make a greater contribution to the human capital development outcome under the National Reform Agenda (NRA), and increase the number of skilled workers in Australia. Data on current vocational and non-vocational ACE programs was analysed. Strategies to improve ACE were collated for consideration by government authorities and ACE providers. There is much diversity in the perceived role and activities of ACE. Researchers have found it challenging to create a profile that depicts the whole sector, particularly in the absence of much reliable, valid and comparable data on ACE activities and outcomes. However, there is evidence indicative of ACE’s assistance in re-engaging with learning and training, and initiating pathways to further training or employment. The potential for ACE to make a bigger contribution to skilling Australia is recognised by governments across the nation (Senate Employment, Workplace Relations, Small Business and Education Committee, 1997). Yet policy changes to facilitate an increased role of ACE in the skilling process, and resourcing for ACE programs continue to receive less attention. This project explored three research questions: • What does the current profile of the ACE sector look like? • How is ACE contributing to reducing the skills deficit? • How can ACE enhance its contributions to reduce the skills deficit and achieve the human capital development outcome of the National Reform Agenda? The responsiveness

ACE research briefing paper 001 : the role of family in new business start-ups

This report uses data from the first two years of the CAUSEE study and focuses on the role of family in new business start-ups. While CAUSEE was not designed specifically to probe deeply into family matters the study does reveal interesting information on family orientated aspects including parental role models, family involvement on the start-up team, and family as a source of funding and advice. These findings can also be related to other information gathered as part of the comprehensive phone interviews that are used to gather the research data for CAUSEE. Furthermore we are also able to compare firm founders and 'Regular' nascent firm and young firm start-ups with their 'High Potential' counterparts in terms of their degrees of family involvement. Unless otherwise stated any differences or effects we comment on are 'statistically significant' at the five per cent level - that is, they are likely to reflect true differences or effects in the entire population of Australian start-ups.

Inhibitors to optimal project portfolio selection

The selection of projects and programs of work is a key function of both public and private sector organisations. Ideally, projects and programs that are selected to be undertaken are consistent with strategic objectives for the organisation; will provide value for money and return on investment; will be adequately resourced and prioritised; will not compete with general operations for resources and not restrict the ability of operations to provide income to the organisation; will match the capacity and capability of the organisation to deliver; and will produce outputs that are willingly accepted by end users and customers. Unfortunately,this is not always the case. Possible inhibitors to optimal project portfolio selection include: processes that are inconsistent with the needs of the organisation; reluctance to use an approach that may not produce predetermined preferences; loss of control and perceived decision making power; reliance on quantitative methods rather than qualitative methods for justification; ineffective project and program sponsorship; unclear project governance, processes and linkage to business strategies; ignorance, taboos and perceived effectiveness; inadequate education and training about the processes and their importance.

Enhancing pathways for ACE learners : Building the capacity of Adult and Community Education (ACE) providers to offer non-accredited courses and VET modules with pathways into VET programs.

This report presents findings from a project that considered a) the current capacity of Adult and Community Education (ACE) providers to offer non-accredited courses and single modules of accredited learning that provide pathways into full scale accredited VET programs, and b) the factors that aid and inhibit this from occurring. Based on the findings, suggestions are made as to what needs to be done to extend this capacity and thereby to achieve the goals outlined in the 2008 Ministerial Declaration on Adult Community Education.

The Australian story : catalysts and inhibitors in the achievement of new women professors

Women are substantially under-represented in the professoriate in Australia with a ratio of one female professor to every three male professors. This gender imbalance has been an ongoing concern with various affirmative action programs implemented in universities but to limited effect. Hence, there is a need to investigate the catalysts for and inhibitors to women’s ascent to the professoriate. This investigation focussed on women appointed to the professoriate between 2005, when a research quality assessment was first proposed, and 2008. Henceforth, these women are referred to as “New Women Professors”. The catalysts and inhibitors in these women’s careers were investigated through an electronic survey and focus group interviews. The survey was administered to new women professors (n=255) and new men professors (n=240) to enable a comparison of responses. However, only women participated in focus group discussions (n=21). An analysis of the survey and interview data revealed that the most critical catalysts for women’s advancement to the professoriate were equal employment opportunities and mentoring. Equal opportunity initiatives provided women with access to traditionally male-dominated forums. Mentoring gave women an insider perspective on the complexity of academia and the politics of the academy. The key inhibitors to women’s career advancement were negative discrimination, the culture of the boys’ club, the tension between personal and professional life, and isolation. Negative discrimination and the boys’ club are problematic because they favour men and marginalise women. The tension between personal and professional life is a particular concern for women who bear children and typically assume the major role in a family for child rearing. Isolation was a concern for both women and men with isolation appearing to increase after ascent to the professoriate. Knowledge of the significant catalysts and inhibitors provides a pragmatic way to orient universities towards redressing the gender balance in the professoriate.

Natural and engineered kallikrein inhibitors: an emerging pharmacopoeia

The kallikreins and kallikrein-related peptidases are serine proteases that control a plethora of developmental and homeostatic phenomena, ranging from semen liquefaction to skin desquamation and blood pressure. The diversity of roles played by kallikreins has stimulated considerable interest in these enzymes from the perspective of diagnostics and drug design. Kallikreins already have well-established credentials as targets for therapeutic intervention and there is increasing appreciation of their potential both as biomarkers and as targets for inhibitor design. Here, we explore the current status of naturally occurring kallikrein protease-inhibitor complexes and illustrate how this knowledge can interface with strategies for rational re-engineering of bioscaffolds and design of small-molecule inhibitors.