ERK-1/2 and p38 in the Regulation of Hypertrophic Changes of Normal Articular Cartilage Chondrocytes Induced by Osteoarthritic Subchondral Osteoblasts

Objective. Previous studies have shown the influence of subchondral bone osteoblasts (SBOs) on phenotypical changes of articular cartilage chondrocytes (ACCs) during the development of osteoarthritis (OA). The molecular mechanisms involved during this process remain elusive, in particular, the signal transduction pathways. The aim of this study was to investigate the in vitro effects of OA SBOs on the phenotypical changes in normal ACCs and to unveil the potential involvement of MAPK signaling pathways during this process. Methods. Normal and arthritic cartilage and bone samples were collected for isolation of ACCs and SBOs. Direct and indirect coculture models were applied to study chondrocyte hypertrophy under the influence of OA SBOs. MAPKs in the regulation of the cell–cell interactions were monitored by phosphorylated antibodies and relevant inhibitors. Results. OA SBOs led to increased hypertrophic gene expression and matrix calcification in ACCs by means of both direct and indirect cell–cell interactions. In this study, we demonstrated for the first time that OA SBOs suppressed p38 phosphorylation and induced ERK-1/2 signal phosphorylation in cocultured ACCs. The ERK-1/2 pathway inhibitor PD98059 significantly attenuated the hypertrophic changes induced by conditioned medium from OA SBOs, and the p38 inhibitor SB203580 resulted in the up-regulation of hypertrophic genes in ACCs. Conclusion. The findings of this study suggest that the pathologic interaction of OA SBOs and ACCs is mediated via the activation of ERK-1/2 phosphorylation and deactivation of p38 phosphorylation, resulting in hypertrophic differentiation of ACCs.

Distributing sensitive information in the MPEG-21 multimedia framework

The MPEG-21 Multimedia Framework provides for controlled distribution of multimedia works through its Intellectual Property Management and Protection ("IPMP") Components and Rights Expression Language ("MPEG REL"). The IPMP Components provide a framework by which the components of an MPEG-21 digital item can be protected from undesired access, while MPEG REL provides a mechanism for describing the conditions under which a component of a digital item may be used and distributed. This chapter describes how the IPMP Components and MPEG REL were used to implement a series of digital rights management applications at the Cooperative Research Centre for Smart Internet Technology in Australia. While the IPMP Components and MPEG REL were initially designed to facilitate the protection of copyright, the applications also show how the technology can be adapted to the protection of private personal information and sensitive corporate information.

Potential of St John's Wort for the treatment of depression : the economic perspective

The burden of rising health care expenditures has created a demand for information regarding the clinical and economic outcomes associated with complementary and alternative medicines. Meta-analyses of randomized controlled trials have found Hypericum perforatum preparations to be superior to placebo and similarly effective as standard antidepressants in the acute treatment of mild to moderate depression. A clear advantage over antidepressants has been demonstrated in terms of the reduced frequency of adverse effects and lower treatment withdrawal rates, low rates of side effects and good compliance, key variables affecting the cost-effectiveness of a given form of therapy. The most important risk associated with use is potential interactions with other drugs, but this may be mitigated by using extracts with low hyperforin content. As the indirect costs of depression are greater than five times direct treatment costs, given the rising cost of pharmaceutical antidepressants, the comparatively low cost of Hypericum perforatum extract makes it worthy of consideration in the economic evaluation of mild to moderate depression treatments.

Public regulatory reform and management earnings forecasts in a low private litigation environment

We examine the impact of continuous disclosure regulatory reform on the likelihood, frequency and qualitative characteristics of management earnings forecasts issued in New Zealand’s low private litigation environment. Using a sample of 720 earnings forecasts issued by 94 firms listed on the New Zealand Exchange before and after the reform (1999–2005), we provide strong evidence of significant changes in forecasting behaviour in the post-reform period. Specifically, firms were more likely to issue earnings forecasts to pre-empt earnings announcements and, in contrast to findings in other legal settings, those earnings forecasts exhibited higher frequency and improved qualitative characteristics (better precision and accuracy). An important implication of our findings is that public regulatory reforms may have a greater benefit in a low private litigation environment and thus add to the global debate about the effectiveness of alternative public regulatory reforms of corporate requirements.

A cyclic porphyrin tetramer linked by azo and butadiyne bridges

A soluble cyclic porphyrin oligomer (CPO) consisting of four 5,10- diarylporphyrins linked by alternating azo and butadiyne bridges has been synthesised via an aminated dinickel(II) butadiyne dimer. This is the first cyclic tetramer that combines both azo and butadiyne bridges and extends the azoporphyrin family, which comprises only a very few examples. The electronic absorption spectrum of the tetramer is more similar to spectra of azoporphyrins than to those of butadiyne-linked dimers or tetramer, exhibiting a two component Soret band with a splitting of 4190 cm-1 and a strongly red-shifted Q band maximum at 735 nm.

Apoptosis is induced in Chlamydia trachomatis infected HEp-2 cells by the addition of a combination innate immune activation compounds and the inhibitor wedelolactone

Problem: Innate immune activation of human cells, for some intracellular pathogens, is advantageous for vacuole morphology and pathogenic viability. It is unknown whether innate immune activation is advantageous to Chlamydia trachomatis viability. ----- ----- Method of study: Innate immune activation of HEp-2 cells during Chlamydia infection was conducted using lipopolysaccharide (LPS), polyI:C, and wedelolactone (innate immune inhibitor) to investigate the impact of these conditions on viability of Chlamydia. ----- ----- Results: The addition of LPS and polyI:C to stimulate activation of the two distinct innate immune pathways (nuclear factor kappa beta and interferon regulatory factor) had no impact on the viability of Chlamydia. However, when compounds targeting either pathway were added in combination with the specific innate immune inhibitor (wedelolactone) a major impact on Chlamydia viability was observed. This impact was found to be due to the induction of apoptosis of the HEp-2 cells under these conditions. ----- ----- Conclusion: This is the first time that induction of apoptosis has been reported in C. trachomatis-infected cells when treated with a combination of innate immune activators and wedelolactone.

A comparison of registered and unregistered organ donors’ perceptions about transplant recipients

Background: We examined whether registered and unregistered donors’ perceptions about transplant recipients’ previous behavior (e.g., substance use) and responsibility for illness differed based on their deceased organ donor registration decisions. ----- ----- ----- Methods: Students and community members from Queensland, Australia were surveyed about their perceptions of transplant recipients.----- ----- ----- Results: Respondents (N = 465) were grouped based on their organ donor registration status to determine if their perceptions about transplant recipients differed. Compared to registered respondents, a higher proportion of unregistered respondents held more negative and less favorable perceptions of recipients. Multivariate analysis of variance confirmed statistically that unregistered respondents evaluated recipients more negatively than registered respondents, F(6,449) = 5.33, p <.001. Unregistered respondents were more likely to view recipients as a smoker, substance user, or alcohol dependent and as undeserving of a transplant, blameworthy, and responsible for their illness. ----- ----- ----- Conclusion: Potential donors’ perceptions of transplant recipients’ behavior and responsibility for illness differ according to their registration status. Future interventions should challenge negative perceptions about recipients’ deservingness and responsibility and promote the perspective that people from all walks of life need transplants in the aim of ultimately encouraging an increase in donor registration.

Defending the sanctity of life principle : a reply to John Keown

This article is a response to Professor Keown’s criticism of my paper “Finding a Way Through the Ethical and Legal Maze: Withdrawal of Medical Treatment and Euthanasia” (2005) 13 (3) Medical Law Review 357. The article takes up and responds to a number of criticisms raised by Keown in an attempt to further the debate concerning the moral and legal status of withdrawing life-sustaining measures, its distinction from euthanasia, and the implications of the lawfulness of withdrawal for the principle of the sanctity of life.

Association between indoor air pollution measurements and respiratory health in women and children in Lao PDR

This article presents the results of a study on the association between measured air pollutants and the respiratory health of resident women and children in Lao PDR, one of the least developed countries in Southeast Asia. The study, commissioned by the World Health Organisation, included PM10, CO and NO2 measurements made inside 181 dwellings in nine districts within two provinces in Lao PDR over a 5- month period (12/05–04/06), and respiratory health information (via questionnaires and peak expiratory flow rate (PEFR) measurements) for all residents in the same dwellings. Adjusted odds ratios were calculated separately for each health outcome using binary logistic regression. There was a strong and consistent positive association between NO2 and CO for almost all questionnaire-based health outcomes for both women and children. Women in dwellings with higher measured NO2 had more than triple of the odds of almost all of the health outcomes, and higher concentrations of NO2 and CO were significantly associated with lower PEFR. This study supports a growing literature confirming the role of indoor air pollution in the burden of respiratory disease in developing countries. The results will directly support changes in health and housing policy in Lao PDR.