Drug development in NZ: can a country be a cluster?

The aims of this research were to assess New Zealand's (NZ) growing drug development industry, and compare it with drug development and biotechnology clusters overseas. This article presents the results of questionnaires administered dutring interviews with 60 senior people representing the industry. It narrates their expertise, knowledge management, and innovative behaviors. NZ's industry comprises highly qualified, very experienced, and motivated people. Their organizations have particular expertise in drug discovery, which has arisen from long‐term government support for biomedical research. There is also significant expertise in early‐stage clinical development and contract clinical research. Knowledge sharing was rated as better within organizations than externally. The participants gave the highest ratings of their organizations' innovative performance to solving problems that had caused others difficulty, teamwork and having new ideas; they prefer informal methods of knowledge acquisition. These factors may reflect the NZ approach of applying ingenuity to solve problems and preference for casual and internal knowledge sharing. NZ has a hub of drug development activity; however, its size, limited resources, and remoteness from major markets may limit the development of a complete pharmaceutical industry. NZ could be promoted as a unique “country cluster” offering niche areas of expertise especially in drug discovery and clinical research. Drug Dev Res 73: 51–58, 2012. © 2011 Wiley Periodicals, Inc.     

Collaboration between infection control and occupational health in three continents: a success story with international impact

Globalization has been accompanied by the rapid spread of infectious diseases, and further strain on working conditions for health workers globally. Post-SARS, Canadian occupational health and infection control researchers got together to study how to better protect health workers, and found that training was indeed perceived as key to a positive safety culture. This led to developing information and communication technology (ICT) tools. The research conducted also showed the need for better workplace inspections, so a workplace audit tool was also developed to supplement worker questionnaires and the ICT. When invited to join Ecuadorean colleagues to promote occupational health and infection control, these tools were collectively adapted and improved, including face-to-face as well as on-line problem-based learning scenarios. The South African government then invited the team to work with local colleagues to improve occupational health and infection control, resulting in an improved web-based health information system to track incidents, exposures, and occupational injury and diseases. As the H1N1 pandemic struck, the online infection control course was adapted and translated into Spanish, as was a novel skill-building learning tool that permits health workers to practice selecting personal protective equipment. This tool was originally developed in collaboration with the countries from the Caribbean region and the Pan American Health Organization (PAHO). Research from these experiences led to strengthened focus on building capacity of health and safety committees, and new modules are thus being created, informed by that work.The products developed have been widely heralded as innovative and interactive, leading to their inclusion into "toolkits" used internationally. The tools used in Canada were substantially improved from the collaborative adaptation process for South and Central America and South Africa. This international collaboration between occupational health and infection control researchers led to the improvement of the research framework and development of tools, guidelines and information systems. Furthermore, the research and knowledge-transfer experience highlighted the value of partnership amongst Northern and Southern researchers in terms of sharing resources, experiences and knowledge.     

Surveillance for azoles resistance in Aspergillus spp. highlights a high number of amphotericin B‐resistant isolates

Aspergillus spp. are the most common invasive mould infection and are responsible for high mortality. Aspergillus fumigatus is currently of interest because resistance to azole antifungals has emerged. The Campinas University Hospital (HC ‐UNICAMP ) receives high‐risk patients susceptible to opportunistic infections but there have been no reports of resistant A. fumigatus . This study aimed to assess the susceptibility profile of Aspergillus isolates, specifically looking for azole resistance. ITS and β‐tubulin DNA sequencing was performed on 228 sequential clinical isolates. Broth microdilution susceptibility testing was performed for all isolates. A. fumigatus represented 74% of the isolates followed by Aspergillus flavus (12%). Nine A. fumigatus isolates from 9 different patients showed high MIC values to at least 1 azole, but cyp51A polymorphisms were detected in only 6 isolates and none correlated with known resistance mutations. The most troubling observation was that the minimum inhibitory concentration for amphotericin B was elevated (≥2 mg L^?1) in 87% of patients with A. flavus isolates and 43% with Aspergillus fumigatus isolates. Given that amphotericin B is used to treat azole‐resistant infections, these data highlight the need for continuous surveillance in Aspergillus for all antifungal resistance to implement correct treatment strategies for the management of these pathogens.     

Peroxisome induction studies on di(2-ethylhexyl)terephthalate

Groups of five male and five female rats were fed diets containing from 0% to 2.5% di(2-ethylhexyl)terephthalate (DEHT) or 1.2% di(2-ethylhexyl)phthalate (DEHP) for 21 days. Feed consumption and body weight gains were collected and, at study termination, animals were examined for alterations in body weight, differences in serum lipids, changes in the activities of certain enzymes associated with fat metabolism, and proliferation of hepatic peroxisomes. Feed consumption and weight gain were greatly decreased in DEHT-fed animals only at 2.5%. No biologically significant alterations in absolute liver weight occurred with DEHT. Relative liver weights were increased at 2.5% in both sexes and at 1.0% and 1.2% in females. The alterations were due wholly to decreased terminal body weights. Serum triglyceride and cholesterol levels were not found useful in interpreting the effects of DEHT. Cyanide-insensitive palmitoyl CoA oxidation and lauric acid 11- and 12-hydroxylation were increased in animals consuming 2.5%, but no lower levels of DEHT. Induction of hepatic peroxisomes did not occur at 1.2% DEHT. Interpretation of minimal peroxisomal effects with 2.5% DEHT was confounded by reduced feed consumption. Slight decreases in weight gain occurred in males consuming the 1.2% DEHP diet, but differences were minor relative to effects observed at 2.5% DEHT. Results with DEHP contrasted with those obtained with DEHT. Absolute and relative liver weights, activities of enzymes of lipid metabolism, and peroxisome content were all significantly increased at 1.2% DEHP. Reduction of feed intake was implicated in the effects observed at 2.5% DEHT, since the amount of DEHT consumed by 2.5% animals was only 1.4 times as much as by 1.2% animals. A possible explanation for the observed differences between DEHP and DEHT was related to the results of a metabolic fate study on DEHT. Metabolism of DEHT by the rat appears to occur via rapid hydrolysis of both ester linkages to give two moles of 2-ethylhexanol and one mole of terephthalic acid. Although 2-ethylhexanol has been shown to induce peroxisome proliferation, it appears to be less active in this respect than the monoester of DEHP. The relatively smaller amounts of monoester produced during the metabolism of DEHT may explain the differences seen in these experiments.     

ASK1 is a novel molecular target for preventing aminoglycoside-induced hair cell death

Journal of Molecular Medicine - Aminoglycoside antibiotics are lifesaving medicines, crucial for the treatment of chronic or drug resistant infections. However, aminoglycosides are toxic to the...     

Micropuncture studies of sodium transport in the remnant kidney of the dog. The effect of graded volume expansion

Proximal and distal tubule micropuncture studies were performed to examine the response to graded extracellular volume (ECV) expansion in 10 normal dogs (stage I), 11 dogs with a unilateral remnant kidney (stage II), and 7 dogs with a remnant kidney after removal of the contralateral kidney (stage III). Before ECV expansion in stage III, there was a suggestive reduction in proximal tubule as well as loop fractional reabsorption of sodium. After ECV expansion to 3% body weight proximal tubule reabsorption was depressed in all groups of animals, while little further inhibition was observed in this segment with additional expansion to 10% body weight. In contrast, the fraction of filtered sodium remaining in the distal tubule rose progressively in all three groups after graded ECV expansion, suggesting that the graded natriuretic response found in the final urine was largely due to a similar response in the loop of Henle rather than that in the proximal tubule. The distal tubule response of the remnant kidney in both stages II and III was greater than that in stage I. These data indicate that although enhanced sodium excretion per nephron in chronic renal failure may be related to uremia, its exaggerated response to ECV expansion is due, at least in part, to certain as yet unidentified intrarenal factors consequent to reduction in functioning renal mass.     

Black and White adults' perspectives on the genetics of nicotine addiction susceptibility

Aims

Emerging research may soon lead to improved quit rates via genetically-tailored smoking cessation treatment. The purpose of this study was to explore individuals' beliefs and attitudes about genetic testing in this context, and how these may differ across racial groups.

Design

Two site qualitative study.

Methods

Eleven focus groups were conducted in 2007 with 51 Black and 55 White adult participants in Montgomery, AL and Baltimore, MD.

Measurements

Questions were asked about smoking as an addiction, the role of genetics in nicotine addiction susceptibility, and undergoing genetic testing to receive tailored smoking cessation treatment. Data were analyzed using content analysis.

Findings

Most participants believed that smoking was an addiction yet were unwilling to endorse the notion that genetics played a role in nicotine addiction susceptibility. However, 91% of White participants and 62% of Black participants indicated that they would likely take a genetic test that would match them to their optimal smoking cessation treatment. The primary potential benefit was a vague sense that additional knowledge about oneself would be of value. Primary barriers included disinterest and skepticism about the test, unwillingness to believe that genetics played a role in nicotine addiction or treatment response, and concerns about psychological consequences.

Conclusions

The majority of participants, particularly Black participants, did not believe that genetics played a significant role in nicotine addiction susceptibility but were willing to undergo genetic testing. Participants identified some benefit to tailoring smoking treatment by genotype. However, participants also expressed skepticism about the test and concerns about its consequences; these issues would need to be addressed in the clinical encounter.