Ion-trapping, microsomal binding, and unbound drug distribution in the hepatic retention of basic drugs

This study investigated the relative contribution of ion-trapping, microsomal binding, and distribution of unbound drug as determinants in the hepatic retention of basic drugs in the isolated perfused rat liver. The ionophore monensin was used to abolish the vesicular proton gradient and thus allow an estimation of ion-trapping by acidic hepatic vesicles of cationic drugs. In vitro microsomal studies were used to independently estimate microsomal binding and metabolism. Hepatic vesicular ion-trapping, intrinsic elimination clearance, permeability-surface area product, and intracellular binding were derived using a physiologically based pharmacokinetic model. Modeling showed that the ion-trapping was significantly lower after monensin treatment for atenolol and propranolol, but not for antipyrine. However, no changes induced by monensin treatment were observed in intrinsic clearance, permeability, or binding for the three model drugs. Monensin did not affect binding or metabolic activity in vitro for the drugs. The observed ion-trapping was similar to theoretical values estimated using the pHs and fractional volumes of the acidic vesicles and the pK(a) values of drugs. Lipophilicity and pK(a) determined hepatic drug retention: a drug with low pK(a) and low lipophilicity (e.g., antipyrine) distributes as unbound drug, a drug with high pK(a) and low lipophilicity (e.g., atenolol) by ion-trapping, and a drug with a high pK(a) and high lipophilicity (e.g., propranolol) is retained by ion-trapping and intracellular binding. In conclusion, monensin inhibits the ion-trapping of high pK(a) basic drugs, leading to a reduction in hepatic retention but with no effect on hepatic drug extraction.

A model for the integration of legal research into Australian undergraduate law curricula

The marginalisation of the teaching and learning of legal research in the Australian law school curriculum is, in the author's experience, a condition common to many law schools. This is reflected in the reluctance of some law teachers to include legal research skills in the substantive law teaching schedule — often the result of unwillingness on the part of law school administrators to provide the resources necessary to ensure that such integration does not place a disproportionately heavy burden of assessment on those who are tempted. However, this may only be one of many reasons for the marginalisation of legal research in the law school experience. Rather than analyse the reasons for this marginalisation, this article deals with what needs to be done to rectify the situation, and to ensure that the teaching of legal research can be integrated into the law school curriculum in a meaningful way. This requires the use of teaching and learning theory which focuses on student-centred learning. This article outlines a model of legal research. It incorporates five transparent stages which are: analysis, contextualisation, bibliographic skills, interpretation and assessment and application.

Spatial inequality in the Australian youth labour market: The role of neighbourhood composition

Australia has experienced a polarization of income and labour market outcomes over the past 20 years (GREGORY and HUNTER, 1995; HARDING, 1996). This has taken an increasingly spatial dimension (HUNTER. 1995a, 1995b), giving rise to concerns that the spatial pooling of disadvantage may hamper the labour market outcomes of youth growing up in poorer residential areas. This paper explores the role that the differential neighbourhood 'quality' of an individual's residential area at age 16 has on their labour market outcomes at age 18 and age 21. Evidence is found that youth who live in poorer quality neighbourhoods face an increased likelihood of being unemployed at both the age of 18 and 21, even after controlling for personal and family characteristics.

Effect of periodontal treatment on the C-reactive protein and proinflammatory cytokine levels in Japanese periodontitis patients

Background: Recent epidemiological studies have shown that individuals with periodontitis have a significantly increased risk of developing coronary heart disease. In addition to conventional risk factors, chronic infection and subsequent production of systemic inflammatory markers may be associated with this increased risk. Objectives: The aim of the present study was to determine whether the presence of chronic periodontitis and subsequent periodontal treatment could influence the serum levels of C-reactive protein (CRP), interleukin-6 and tumor necrosis factor-alpha (TNF-alpha) in a Japanese population. Methods: Sera were obtained from 24 patients with moderate to advanced periodontitis at the baseline examination and at reassessment after completion of treatment. As a control, sera were also obtained from 21 subjects without periodontitis. High-sensitivity CRP (hs-CRP) was measured using nephelometry with a latex particle-enhanced immunoassay and interleukin-6 and TNF-alpha were determined by sensitive enzyme-linked immunosorbent assay. Results: The levels of hs-CRP and interleukin-6 in the sera of this Japanese population seemed to be much lower than those reported in other populations. TNF-alpha on the other hand, demonstrated similar levels between this Japanese and other populations. Periodontal status demonstrated a significant improvement in all patients following treatment. There was a trend toward higher hs-CRP levels in patients at baseline compared with control subjects. Hs-CRP level tended to decrease with improvement of the periodontal condition following treatment and approached that of control subjects, although this decline was not statistically significant. interleukin-6 and TNF-alpha levels did not change following periodontal treatment. Furthermore, there was no difference in the serum levels of these inflammatory cytokines between patients either at baseline or at reassessment and control subjects. Conclusions: In this pilot study, we were unable to show that periodontal disease significantly affects the serum levels of systemic inflammatory markers. However, this does not necessarily mean that periodontitis does not contribute to the total burden of inflammation as there was a tendency for hs-CRP to decrease following successful periodontal treatment. Large-scale studies are clearly needed to determine the impact of periodontal disease on systemic inflammation.

Outbound Travel Depends on Business Returns: Australian Evidence

In an earlier note, Collins and Tisdell (2002b) explored the possibility of a long-run relationship between Australian business returns and international business travel. Using annual data they found that such a relationship exists. The purpose of this study is to further examine this relationship using quarterly data for the time frame 1974:1 to 1999:4. In addition, previous studies on international business travel have offered some but not strong evidence for the existence of a positive relationship between the level of international business travel and real GDP of the origin country. This study suggests that the aggregate return on business investments is a better predictor of international business travel than GDP. The Engle-Granger and Johansen's maximum-likelihood cointegration procedures are used to show a long-term relationship exists between Australian outbound business travel and Australian business returns, but not with Real Australian GDP. Reasons for this relationship are discussed.

Host-dependent Anopheles flavirostris larval distribution reinforces the risk of malaria near water

Malaria control strategies are more likely to be successful if groups at high risk can be accurately predicted. Given that mosquitoes have an obligate aquatic phase we were interested in determining how vector larval abundance relates to the spatial distribution of human malaria infection. We examined the relationship between malaria parasite prevalence and distance from vector larval habitat, and vector larval abundance and distance from human habitation, in separate studies in rural, low-endemic areas of the Philippines. Parasite prevalence among symptomatic patients was significantly higher among those living in proximity ( less than or equal to 50 m) to potential larval habitats of the major vector, Anopheles flavirostris (adjusted odds ratio [AOR] 2.64, P = 0.02 and AOR 3.43, P = 0.04). A larval survey of A. flavirostris revealed a higher density of early and late instars near human habitation (adjusted P < 0.05). The results suggest that larvae are associated with human habitation, thereby reinforcing malaria risk in people living close to larval habitats. This has implications for understanding the interaction between vectors, hosts, and parasites, and the potential for success of localized malaria control measures.

Disabled e-nation: Telecommunications, disability, and national policy

This article considers questions of technological change, innovation, and communication from a disability perspective. Using a critical social perspective on disability, we offer an Australian case study to analyse disability in national telecommunications policy. In doing so, we critique the systemic lack of incorporation of disability in national visions, policies, and programmes. Accordingly, we argue for a cohesive, and genuine commitment to incorporating disability considerations in all areas of information and communication technology policy and scholarship.

When tomorrow finally comes: Imagining disability

The article focuses on scholars with disabilities reimagining communication. The trans disciplinary department of Communication, Cultural, and Media Studies in an Australasian university lies within a university that routinely asks what members of the university community need for functioning, and provides the communication facilitation, attendant and personal care, and other support, seeking to integrate these with community support, without seeking to place the financial burden of such support upon the individual or their family. Significant research projects are conducted with, and within, diverse communities, with which the university has equal and continuing relationships, as well as in the everyday interactions on campus, in the virtual communities fostered within the department, and with the wider community. Disability and deafness studies, have become an essential part of the teaching and learning as well as the research program. However, rather than some grand scenario being the epitome, it is in the day to day relationships of scholars and students drawn from communication, cultural, and media studies and people with disability.

Uniting the nation? Disability, stem cells, and the Australian media

In this article, the 2002 Australian debate regarding embryonic stem cells is examined. This shows the importance of an analysis of the media to understanding how disability is constructed in discourses of nationhood and biotechnology. Media representation of disability-for instance, signifying disability as catastrophe-is seen as crucial in securing access to a variety of biotechnologies, such as embryonic stem cells. Analysis of such media moments shows a structure of privileged and excluded voices in debates regarding disability and biotechnology. The diversity of voices in the Australian community regarding disability is not represented in a range of media, nor are people with disability quoted as experts on disability. A recognition of the media's construction of disability must be matched by a commitment to disability as part of a truly civil society. It is only in this way that we will have biotechnologies, and diverse cultural and media representations that meet the requirements of the international disability rights movement motto of 'nothing about us without us', recently emphasized in the Disabled Peoples' International Europe's 2000 statement on biotechnology.

Medicinal herbal extracts - renal friend or foe? Part one: The toxicities of medicinal herbs

In recent years, an increasing percentage of people from industrialized countries have been using complementary and alternative medicines (CAM). This, combined with numerous warnings regarding the potential toxicity of these therapies, suggests the need for practitioners to keep abreast of the reported incidence of renal toxicity caused by the ingestion of medicinal herbs. The goal of the present two-part series, on the toxic or beneficial effects of medicinal herbs on renal health, is to provide practitioners with a summary of the most recent information as well as the means by which evidence for benefit or toxicity has been found. In this first article, we explore in vivo evidence of toxicity. Included are nephrotoxicity from aristolochic acid and other components within herbs, herb-drug interactions resulting in adverse renal effects, and renal toxicity from contaminants within the extracts. The review aims to provide a guide to encourage future toxicity studies and rigorous clinical trials.