Effect of post-mortem changes on peripheral and central whole blood and tissue clozapine and norclozapine concentrations in the domestic pig (Sus scrofa)

Interpretation of the results of psychoactive or other drug measurements in post-mortem blood specimens may not be straightforward, in part because analyte concentrations in blood may change after death. There is also the issue of comparability of plasma (or serum) results to those obtained in whole blood. To investigate these problems with respect to clozapine, this drug (10mg/kg daily) was given orally to two pigs. Blood was collected 3h post-dose on day 7, the animals were sacrificed, and blood taken from central and peripheral veins for up to 48 h after death. Tissue samples were also collected immediately after death and at 48 h. Ante-mortem whole blood clozapine/N-desmethylclozapine (norclozapine) concentrations were 0.86/1.07 and 1.11/1.15 mg/l in pigs 1 and 2, respectively. Blood clozapine and norclozapine concentrations generally increased after death (central vein: clozapine up to 300%, norclozapine up to 460%; peripheral vein: clozapine up to 155%, norclozapine up to 185%). Initial blood and kidney clozapine and norclozapine concentrations were comparable in both animals, but were some two-fold higher in heart, liver and striated muscle in pig 2. In both animals, the heart and striated muscle clozapine and norclozapine concentrations had increased some two- to three-fold at 48 h, whilst the liver and kidney concentrations were essentially unchanged. The reason for the increase in heart and striated muscle concentrations at 48 h is unclear, but could be simple variation in sample site. The plasma:whole blood distribution of clozapine and norclozapine was studied in vitro. In human blood (one volunteer donor, haematocrit 0.50) the plots of plasma versus whole blood concentration were linear for both analytes across the range 0.1-1.5mg/l, although clozapine favoured plasma (plasma:whole blood ratio=1.12), whereas norclozapine favoured whole blood (ratio 0.68). In pig blood, the plots of plasma versus whole blood were non-linear in both cases, although clozapine favoured plasma to a greater extent than norclozapine. This may be due to lower plasma clozapine and norclozapine protein binding capacity in the pig as compared to man.     

Dimensions of state disruption and international responses

In the post-Cold War period there has been a dramatic increase in the number of states which can be classified as disrupted, thus creating a major source of political, social and military turbulence and instability in world politics. The causes have been varied, ranging from the fragmentation of the national elite and breakdown of social order, ethnic antagonisms, ideological struggle, confessional or sectarian strife to legitimacy crises and separatism. This has focused attention once again on the future of the international system. This paper considers the nature of disrupted states, the external and internal sources of the disruption, and the options that are available to the international community, in particular whether there is an appropriate role for the United Nations.     

Special and Differential Treatments provisions in the TRIPs negotiations

Legal context: This article reviews the current status of World Trade Organization(WTO) negotiations on Special and Differential Treatments (S&DT)of developing countries in TRIPs, referred to here as the agreementon compulsory licensing. Key points: The main thrust of the article is that, although the negotiationshave reached equilibrium, there are still some open questionswhich may prove problematic in the future. Practical significance: The most important remaining question to be borne in mind bypractitioners is how the results reached might be incorporatedin TRIPs and made permanent, this impacting future pratice.     

Anomie at public organizations: How can the quality of work life help?

Will enhancing the quality of work life impact the reduction of anomic behaviors at work in public sector organizations? To answer this question, we examined the impact of three structural, managerial, and social dimensions of the quality of work life, including the employees' anomie behaviors at the workplace. A cross‐sectional survey data were collected from 250 employees working in the public sector organizations located in the Kerman Province, (southeast) Iran. Our findings support the negative effects that the three dimensions of quality of work life have on employees' anomic behaviors. The results of this study highlighted the importance that the quality of work life has on reducing unethical and immoral behavior among employees in public organizations.     

Vulnerability to Multi-Dimensional Poverty: An Empirical Comparison of Alternative Measurement Approaches

This paper investigates whether different measures of ex-post poverty and ex-ante vulnerability to poverty provide consistent estimates of poverty and vulnerability to poverty across households. Moreover, if there is some heterogeneity in the identification of households as poor and vulnerable, it investigates the degree of mismatch between measures? The ex-post monetary poverty (MP) and multidimensional poverty (MDP) measures are used to identify poor households. Likewise, the ex-ante vulnerability to monetary poverty (VMP) and vulnerability to multidimensional poverty (VMDP) measures are used to identify vulnerable households. Using a large household survey data-set of about 90,000 households from the Punjab province of Pakistan, we find that most of the vulnerable households are accurately identified by the ex-ante measures of vulnerability to poverty. However, the ex-post measures of poverty identify different households as poor. Our results show that 18 percent households experiencing MDP are not captured by the one-dimensional measure of MP. The important implication of this study is that the choice of measures does matter in ex-post poverty identification, but not as much in the identification of ex-ante vulnerability to poverty.