In vitro evaluation of differences in phase 1 metabolism of ketamine and other analgesics among humans, horses, and dogs

OBJECTIVE: To investigate cytochrome P450 (CYP) enzymes involved in metabolism of racemic and S-ketamine in various species and to evaluate metabolic interactions of other analgesics with ketamine. SAMPLE POPULATION: Human, equine, and canine liver microsomes. PROCEDURES: An analgesic was concurrently incubated with luminogenic substrates specific for CYP 3A4 or CYP 2C9 and liver microsomes. The luminescence signal was detected and compared with the signal for negative control samples. Ketamine and norketamine enantiomers were determined by use of capillary electrophoresis. RESULTS: A concentration-dependent decrease in luminescence signal was detected for ibuprofen and diclofenac in the assay for CYP 2C9 in human and equine liver microsomes but not in the assay for CYP 3A4 and methadone or xylazine in any of the species. Coincubation of methadone or xylazine with ketamine resulted in a decrease in norketamine formation in equine and canine liver microsomes but not in human liver microsomes. In all species, norketamine formation was not affected by ibuprofen, but diclofenac reduced norketamine formation in human liver microsomes. A higher rate of metabolism was detected for S-ketamine in equine liver microsomes, compared with the rate for the S-enantiomer in the racemic mixture when incubated with any of the analgesics investigated. CONCLUSIONS AND CLINICAL RELEVANCE: Enzymes of the CYP 3A4 family and orthologs of CYP 2C9 were involved in ketamine metabolism in horses, dogs, and humans. Methadone and xylazine inhibited in vitro metabolism of ketamine. Therefore, higher concentrations and diminished clearance of ketamine may cause adverse effects when administered concurrently with other analgesics.

Tackling Youth Exclusion in the UK: Challenges for Current Policy and Practice

Addressing the situation of marginalised youth has been central to policy initiatives directed at tackling poverty and social exclusion in the UK in recent years. The period since 1997 has therefore witnessed a renewed emphasis upon the development of a coherent framework for youth policy in the UK with the goal of promoting youth inclusion and participation. Nevertheless, understanding the nature and prospects for policies designed to tackle youth exclusion involves a deeper interrogation of the concept of ‘social exclusion’ and its applications within UK policy debates. Here, it is argued that whilst considerable progress has been made in the promotion of a coherent and integrated strategy for youth inclusion in the UK such policies are unlikely to be effective without a re-conceptualisation of the nature of social exclusion, its causes and consequences. In particular, a more holistic understanding is called for which extends beyond an emphasis on labour market activation policies as a response to the circumstances facing marginalised youth in the UK and elsewhere, and one which interrogates exclusionary processes and institutional practices rather than addressing only the symptoms of disadvantage.

Homelessness, Social Work, Social Policy and the Print Media in Australian Cities

Homelessness is a significant social problem worldwide. This paper describes an Australian study that examined print media representations of homelessness and social work, social policy and social work responses to homelessness in three Australian cities. The research included a content analysis of seven Australian newspapers and semi-structured interviews with 39 social workers employed in the field of homelessness in Adelaide, Melbourne and Sydney. The detailed results of these studies have been published separately elsewhere. This paper reports on how discourses in the print media, social policy and social work practice co-exist in constructing homelessness as a particular social problem, influencing social work responses to homelessness. The research found that individualism is central to many dominant discourses evident in the print media, social policy and social work practice, and that social work is practiced within unequal power relations embedded in organisational contexts.

Unconventional Monetary Policy and the Great Recession: Estimating the Macroeconomic Effects of a Spread Compression at the Zero Lower Bound

We explore the macroeconomic effects of a compression in the long-term bond yield spread within the context of the Great Recession of 2007–09 via a time-varying parameter structural VAR model. We identify a “pure” spread shock defined as a shock that leaves the policy rate unchanged, which allows us to characterize the macroeconomic consequences of a decline in the yield spread induced by central banks’ asset purchases within an environment in which the policy rate is constrained by the effective zero lower bound. Two key findings stand out. First, compressions in the long-term yield spread exert a powerful effect on both output growth and inflation. Second, conditional on available estimates of the impact of the Federal Reserve’s and the Bank of England’s asset purchase programs on long-term yield spreads, our counterfactual simulations suggest that U.S. and U.K. unconventional monetary policy actions have averted significant risks both of deflation and of output collapses comparable to those that took place during the Great Depression.

Strategic trade policy and non-linear subsidy : in the case of price competition

In a strategic trade policy, it is assumed, in this paper, that a government changes disbursement or levy method so that the reaction function of home firm approaches infinitely close to that of foreign firm. In the framework of Bertrand-Nash equilibrium, Eaton and Grossman[1986] showed that export tax is preferable to export subsidy. In this paper, it is shown that export subsidy is preferable to export tax in some cases in the framework of Bertrand-Nash equilibrium, considering the uncertainty in demand. Historically, many economists mentioned non-linear subsidy or tax. However, optimum solution of it has not yet been shown. The optimum solution is shown in this paper.

The stakes of politics and electoral administration : a comparative study of Southeast Asian democracies

Elections play a crucial role in political stability in post-democratization, and electoral administrations are the key to the electoral process. However, not all newly democratized countries have established reliable electoral administration. New democracies in Southeast Asia, such as the Philippines, Indonesia and Thailand, have independent election commissions which have different characteristics, especially in terms of neutrality. Based on three cases, this paper claims that the stakes of politics are the major determinant of the variations in neutrality. The high stakes of politics in Thailand brought about the partisan election commission, while the low stakes in Indonesia made the electoral system relatively neutral. Like Thailand, the high stakes of politics in the Philippines also cause political intervention in the electoral administration.