The global biopharma industry and the rise of Indian drug multinationals: implications for Australian generics policy

This article provides a synopsis of the new dynamics of the global biopharma industry. The emergence of global generics companies with capabilities approximating those of 'big pharma' has accelerated the blurring of boundaries between the innovator and generics sectors. Biotechnology-based products form a large and growing segment of prescription drug markets and regulatory pathways for biogenerics are imminent. Indian biopharma multinationals with large-scale efficient manufacturing plants and growing R&D capabilities are now major suppliers of Active Pharmaceutical Ingredients (APIs) and generic drugs across both developed and developing countries. In response to generic competition, innovator companies employ a range of life cycle management techniques, including the launch of 'authorised generics'. The generics segment in Australia will see high growth rates in coming years but the prospect for local manufacturing is bleak. The availability of cheap generics in international markets has put pressure on Pharmaceutical Benefits Scheme (PBS) pricing arrangements, and a new policy direction was announced in November 2006. Lower generics prices will have a negative impact on some incumbent suppliers but industrial renewal policies for the medicines industry in Australia are better focused on higher value R&D activities and niche manufacturing of sophisticated products

The Base Excision Repair System of Salmonella enterica serovar Typhimurium Counteracts DNA Damage by Host Nitric Oxide

Intracellular pathogens must withstand nitric oxide (NO·) generated by host phagocytes. Salmonella enterica serovar Typhimurium interferes with intracellular trafficking of inducible nitric oxide synthase (iNOS) and possesses multiple systems to detoxify NO·. Consequently, the level of NO· stress encountered by S. Typhimurium during infection in vivo has been unknown. The Base Excision Repair (BER) system recognizes and repairs damaged DNA bases including cytosine and guanine residues modified by reactive nitrogen species. Apurinic/apyrimidinic (AP) sites generated by BER glycosylases require subsequent processing by AP endonucleases. S. Typhimurium xth nfo mutants lacking AP endonuclease activity exhibit increased NO· sensitivity resulting from chromosomal fragmentation at unprocessed AP sites. BER mutant strains were thus used to probe the nature and extent of nitrosative damage sustained by intracellular bacteria during infection. Here we show that an xth nfo S. Typhimurium mutant is attenuated for virulence in C3H/HeN mice, and virulence can be completely restored by the iNOS inhibitor L-NIL. Inactivation of the ung or fpg glycosylase genes partially restores virulence to xth nfo mutant S. Typhimurium, demonstrating that NO· fluxes in vivo are sufficient to modify cytosine and guanine bases, respectively. Mutants lacking ung or fpg exhibit NO·–dependent hypermutability during infection, underscoring the importance of BER in protecting Salmonella from the genotoxic effects of host NO·. These observations demonstrate that host-derived NO· damages Salmonella DNA in vivo, and the BER system is required to maintain bacterial genomic integrity

KINS 499 Mouthguard Use on Throwing Velocity

Successful pitching in baseball may be due to several factors including the mechanics of the motion, the strength, power, flexibility of the athlete, as well as their intent and fatigue levels. The pitching motion is a very powerful, violent, complex and abnormal range of motion of the body. In recent studies, it has been widely evidenced that the ability to produce instantaneous high peak force outputs is related to success in sport. Therefore, the ability to produce higher peak force may be related to the ability to pitching in baseball. Mouthguards have been shown to significantly increase power production in several dynamic exercise movements. The purpose of this study was to determine if maximal and average pitching velocity could be increased when wearing a mouthguard. Twenty-two male collegiate baseball pitchers participated in this study (age: 19.9 years old ± 1.4 years, body mass: 87.1 Kg ± 11.6 Kg, body height: 182.5 cm ± 6.1 cm). All study participants were competitive athletes at the NCAA Division 1, Division 3, or University Varsity Club level. Pitching velocity changes resulted in a mean increase of 0.732 km/h for all groups. Velocity change for each level tested resulted in mean increases of 1.652, 0.402, and 0.370 km/h for the university club, Division 3 and Division 1 levels, respectively. The results of a paired samples t-test analysis showed that there was a statistically significant improvement when using a mouthguard in pitching velocity across all groups combined; t (109) = 2.958, p = 0.004. Further, university club level pitchers experienced a statistically significant improvement; t(29) = 5.972, p = 0.000; while Division 3; t(39) = 0.772, p = 0.445; and Division 1; t(39) = 1.014, p = 0.317; players did not show a statistically significant improvement with the mouthguard. The authors found that a mouthguard may improve throwing velocity in male collegiate baseball athletes. These findings could be useful to both coaches and sport performance specialists that are working with pitchers to bring about increases in power output and subsequent increases in pitching velocity, simply by implementing the use of a mouthguard