Validation of Large White Pig as an animal model for the study of cannabinoids metabolism: application to the study of THC distribution in tissues

This study presents a new animal model, the Large White Pig, which was tested for studying cannabinoids metabolism. The first step has focused on determination of plasma kinetics after injection of Delta(9)-tetrahydrocannabinol (THC) at different dosages. Seven pigs received THC by intravenous injections (50, 100 or 200 microg/kg). Plasma samples were collected during 48 h. Determination of cannabinoids concentrations were performed by gas chromatography/mass spectrometry. Results showed that plasma kinetics were comparable to those reported in humans. Terminal half-life of elimination was 10.6 h and a volume of distribution of 32 l/kg was calculated. In a second step, this model was used to determine the kinetic profile of cannabinoids distribution in tissues. Eight Large White male pigs received an injection of THC (200 microg/kg). Two pigs were sacrificed 30 min after injection, two others after 2, 6 and 24 h. Different tissues were sampled: liver, kidney, heart, lung, spleen, muscle, fat, bile, blood, vitreous humor and several brain areas. The fastest THC elimination was noted in liver tissue, where it was completely eliminated in 6 h. THC concentrations decreased in brain tissue slower than in blood. The slowest THC elimination was observed for fat tissue, where the molecule was still present at significant concentrations 24 h later. After 30 min, THC concentration in different brain areas was highest in the cerebellum and lowest in the medulla oblongata. THC elimination kinetics noted in kidney, heart, spleen, muscle and lung were comparable with those observed in blood. 11-Hydroxy-THC was only found at high levels in liver. THC-COOH was less than 5 ng/g in most tissues, except in bile, where it increased for 24 h following THC injection. This study confirms, even after a unique administration, the prolonged retention of THC in brain and particularly in fat, which could be at the origin of different phenomena observed for heavy users such as prolonged detection of THC-COOH in urine or cannabis-related flashbacks. Moreover, these results support the interest for this animal model, which could be used in further studies of distribution of cannabinoids in tissues.     

Why we must end insurance discrimination against mental health care

In this Policy Essay, Representative Patrick Kennedy argues that insurance discrimination against those suffering from mental illness constitutes a serious and often overlooked deficiency of the modern American health care system. While the Mental Health Parity Act of 1996 was an important step toward resolutions of this issue, many loopholes remain that allow insurance companies to deny much-needed coverage to those suffering from such illnesses. This Essay details how improving access to health insurance for the mentally ill is not only socially beneficial, but also economically sound; the cost of instituting mental health parity is far outweighed by the costs that employers bear because of the reduced productivity of untreated mental illness sufferers. Representative Kennedy recommends that these problems may be addressed by additional mental health policy legislation--specifically, the proposed Paul Wellstone Act.     

Developmental validation of a single-tube amplification of the 13 CODIS STR loci, D2S1338, D19S433, and amelogenin: the AmpFlSTR Identifiler PCR Amplification Kit

Analysis of length polymorphism at short tandem repeat (STR) loci utilizing the polymerase chain reaction (PCR) process has proven to be an ideal assay for human identification purposes. The short length of STR loci coupled with the amplification of target sequence through PCR allows for a robust, sensitive, and specific assay for highly polymorphic markers. A multiplex containing fifteen STR loci plus the gender-determining locus Amelogenin was developed to provide a single amplification/detection of all CODIS (Combined DNA Index System) STR loci (CSF1PO, D3S1358, D5S818, D7S820, D8S1179, D13S317, D16S539, D18S51, D21S11, FGA, TH01, TPOX, and vWA) as well as two internationally-accepted STRs (D2S1338 and D19S433). By incorporating five-dye fragment analysis technology and non-nucleotide linkers, previously optimized AmpFlSTR kit primer sequences have been maintained. This kit has been developed in accordance with the standards of the forensic community as defined by the DNA Advisory Board. Validation studies were performed to include developmental validation, and the results support the use of the AmpFlSTR Identifiler PCR Amplification Kit for human identity and parentage testing.     

What Drives Machinery of Government Change? Australia,Canada and the United Kingdom, 1950–1997

Machinery of government arrangements attract a diverse and detailed literature, but surprisingly little comparative research. This article provides a graphically presented indication of functional changes in the architecture of national government in Australia, Canada and the United Kingdom between 1950 and 1997. An analysis finds interesting national differences, with sharp changes in practice in Australia and Canada, but more gradual incremental adjustment in the United Kingdom. The correlation between parties and machinery change is weak for Canada and the United Kingdom, but all countries demonstrate stronger links between elections, new prime ministers and machinery of government changes. Further, all tend to oscillate between many specialist departments and fewer, broader agencies
The explanation for such machinery change, we argue, is found in the political, policy and administrative calculations made by prime ministers in Westminster-style parliamentary systems     

Variations in the Use of Grant Discretion: The Case of ISTEA

The Intermodal Surf ace Transportation Efficiency Act gave stategovernments increased flexibility in spending federal transportationgrant funds. However, most of the flexibility was not used;there are many other potential sources of inflexibility in transportationpolicymaking. States were more likely to use flexibility ifthey were politically liberal, had larger populations and, otherthings being equal, had less metropolitan populations. Statesthat were previously more involved in nontraditional transportationprograms were also somewhat more likely to use flexibility.