Repositioning "old" drugs for new causes : identifying new treatments for prostate cancer

The majority of prostate cancer related deaths are due to the spread of the disease. This project developed a screening protocol to identify existing drugs that could be used to prevent the spread of prostate cancer and thereby improve the survival of the patients.

The use of prescribed drugs for common chronic conditions in South Africa in 1998

Purpose To determine the prescribed drug-utilisation pattern for six common chronic conditions in adult South Africans in a cross-sectional survey. Methods 13 826 randomly selected participants, 15 years and older, were surveyed by trained fieldworkers at their homes in 1998. Questionnaires included socio-demographic, chronic-disease and drug-use data. The prescribed drugs were recorded from participants' medication containers. The Anatomical Therapeutic Classification (ATC) code of the drugs for tuberculosis (TB), diabetes, hypertension, hyperlipidaemia, other atherosclerosis-related conditions, such as heart conditions or cerebrovascular accidents (CVA), and asthma or chronic obstructive pulmonary disease (COPD), was recorded. The use of logistic regression analyses identified the determinants of those patients who used prescription medication for these six conditions. Results 18.4% of the women and 12.5% of the men used drugs for the six chronic conditions. Men used drugs most frequently for hypertension (50.9%) and asthma or chronic bronchitis (24.3%), while in women it was for hypertension (59.9%) and diabetes (17.5%). The logistic regression analyses showed that women, wealthier and older people, and those with medical insurance used these chronic-disease drugs more frequently compared to men, younger or poor people, or those without medical insurance. The African population group used these drugs less frequently than any other ethnic group. The inappropriate use of methyldopa was found for 14.8% of all antihypertensive drugs, while very few people used aspirin. Conclusions The methodology of this study provides a means of ascertaining the chronic-disease drug-utilisation pattern in national health surveys. The pattern described, suggests an inequitable use of chronic-disease drugs and inadequate use of some effective drugs to control the burden of chronic diseases in South Africa. Copyright © 2004 John Wiley & Sons, Ltd.

Do we need a law to help people try experimental drugs?

People with life-threatening or incurable diseases may be willing to try experimental drugs and unproven treatments, but they face the risk of exploitation. Is the law the best avenue to ensure that they are protected while medical innovation is encouraged? Protection of vulnerable people is a thread running through many laws, in Australia and elsewhere. In medical law, for instance, children and people with impaired decision-making capacity warrant special attention. But what of the ordinary person diagnosed with a life-threatening disease? Such people are vulnerable to harm and potential exploitation when they seek access to innovative, experimental or unproven treatments that depart from the existing range of accepted medicine.

The high price of drug patents: Australia, patent law, pharmaceutical drugs and the Trans-Pacific Partnership

This week, the secrecy surrounding an independent Australian report on patent law and pharmaceutical drugs has been lifted, and the work has been published to great acclaim...

Using quantitative wastewater analysis to measure daily usage of conventional and emerging illicit drugs at an annual music festival

Introduction and Aims Wastewater analysis provides a non-intrusive way of measuring drug use within a population. We used this approach to determine daily use of conventional illicit drugs [cannabis, cocaine, methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA)] and emerging illicit psychostimulants (benzylpiperazine, mephedrone and methylone) in two consecutive years (2010 and 2011) at an annual music festival. Design and Methods Daily composite wastewater samples, representative of the festival, were collected from the on-site wastewater treatment plant and analysed for drug metabolites. Data over 2 years were compared using Wilcoxon matched-pair test. Data from 2010 festival were compared with data collected at the same time from a nearby urban community using equivalent methods. Results Conventional illicit drugs were detected in all samples whereas emerging illicit psychostimulants were found only on specific days. The estimated per capita consumption of MDMA, cocaine and cannabis was similar between the two festival years. Statistically significant (P < 0.05; Z = −2.0–2.2) decreases were observed in use of methamphetamine and one emerging illicit psychostimulant (benzyl piperazine). Only consumption of MDMA was elevated at the festival compared with the nearby urban community. Discussion and Conclusions Rates of substance use at this festival remained relatively consistent over two monitoring years. Compared with the urban community, drug use among festival goers was only elevated for MDMA, confirming its popularity in music settings. Our study demonstrated that wastewater analysis can objectively capture changes in substance use at a music setting without raising major ethical issues. It would potentially allow effective assessments of drug prevention strategies in such settings in the future.

In vivo evaluation of folate decorated cross-linked micelles for the delivery of platinum anticancer drugs

The biodistribution of micelles with and without folic acid targeting ligands were studied using a block copolymer consisting of acrylic acid (AA) and polyethylene glycol methyl ether acrylate (PEGMEA) blocks. The polymers were prepared using RAFT polymerization in the presence of a folic acid functionalized RAFT agent. Oxoplatin was conjugated onto the acrylic acid block to form amphiphilic polymers which, when diluted in water, formed stable micelles. In order to probe the in vivo stability, a selection of micelles were cross-linked using 1,8-diamino octane. The sizes of the micelles used in this study range between 75 and 200 nm, with both spherical and worm-like conformation. The effects of cross-linking, folate conjugation and different conformation on the biodistribution were studied in female nude mice (BALB/c) following intravenous injection into the tail vein. Using optical imaging to monitor the fluorophore-labeled polymer, the in vivo biodistribution of the micelles was monitored over a 48 h time-course after which the organs were removed and evaluated ex vivo. These experiments showed that both cross-linking and conjugation with folic acid led to increased fluorescence intensities in the organs, especially in the liver and kidneys, while micelles that are not conjugated with folate and not cross-linked are cleared rapidly from the body. Higher accumulation in the spleen, liver, and kidneys was also observed for micelles with worm-like shapes compared to the spherical micelles. While the various factors of cross-linking, micelle shape, and conjugation with folic acid all contribute separately to prolong the circulation time of the micelle, optimization of these parameters for drug delivery devices could potentially overcome adverse effects such as liver and kidney toxicity.

Critical review on the stability of illicit drugs in sewers and wastewater samples

Wastewater-based epidemiology (WBE) applies advanced analytical methods to quantify drug residues in wastewater with the aim to estimate illicit drug use at the population level. Transformation processes during transport in sewers (chemical and biological reactors) and storage of wastewater samples before analysis are expected to change concentrations of different drugs to varying degrees. Ignoring transformation for drugs with low to medium stability will lead to an unknown degree of systematic under- or overestimation of drug use, which should be avoided. This review aims to summarize the current knowledge related to the stability of commonly investigated drugs and, furthermore, suggest a more effective approach to future experiments. From over 100 WBE studies, around 50 mentioned the importance of stability and 24 included tests in wastewater. Most focused on in-sample stability (i.e., sample preparation, preservation and storage) and some extrapolated to in-sewer stability (i.e., during transport in real sewers). While consistent results were reported for rather stable compounds (e.g., MDMA and methamphetamine), a varying range of stability under different or similar conditions was observed for other compounds (e.g., cocaine, amphetamine and morphine). Wastewater composition can vary considerably over time, and different conditions prevail in different sewer systems. In summary, this indicates that more systematic studies are needed to: i) cover the range of possible conditions in sewers and ii) compare results more objectively. To facilitate the latter, we propose a set of parameters that should be reported for in-sewer stability experiments. Finally, a best practice of sample collection, preservation, and preparation before analysis is suggested in order to minimize transformation during these steps.

Safety impacts of alcohol and other drugs in construction

Estimated 638,400 persons suffered a work-related injury or illness in 2009-2010 and 337 lost their lives as a result in 2009-2010. In 2013-2014, there were 186 fatalities with 29 (16%) occurring in construction. Very little is known about what proportion of accidents are directly attributable to the effects of AOD. Anecdotal evidence highlights issues of AOD and its association with safety risk on construction sites. Research Objective: • To scientifically evaluate the relationship between the use of AOD and the safety impacts within the Australian construction industry to engender a cultural change in the workforce • A nationally consistent and collaborative approach involving government, employers and employees, unions and other key industry stakeholders

Heparin/heparan sulphate-based drugs

Glycosaminoglycans (GAGs) are an untapped source of novel chemical entities and, therefore, offer exciting new opportunities for the development of novel drug molecules because of their unique physical and biological properties. Advances in the functional understanding of GAG–protein interactions are enabling the development of GAG mimetics for use as anti-angiogenic, anti-metastatic, anti-inflammatory, anticoagulant and anti-thrombotic agents. Many anti-thrombotic molecules, such as Fondaparinux and Idraparinux, have been successful in clinical trials, and a new generation of heparin mimetic oligosaccharides and small molecules are currently in different stages of clinical development. In particular, the recent increased activity in the development of new mimetics by altering the composition of sulphated GAGs is very encouraging. This article reviews structurally defined heparin-mimetic oligosaccharides and small molecules currently in development or clinical trials...