Chromatographic analysis and survey studies to evaluate the emerging drugs of synthetic cannabinoids in Scotland and Saudi Arabia

Synthetic cannabinoid receptor agonists or more commonly known as synthetic cannabinoids (SCs) were originally created to obtain the medicinal value of THC but they are an emerging social problem. SCs are mostly produced coated on herbal materials or in powder form and marketed under a variety of brand names, e.g. “Spice”, “K2”. Despite many SCs becoming controlled under drug legislation, many of them remain legal in some countries around the world. In Scotland, SCs are controlled under the Misuse of Drugs Act 1971 and Psychoactive Substances Act 2016 that only cover a few early SCs. In Saudi Arabia, even fewer are controlled. The picture of the SCs-problem in Scotland is vague due to insufficient prevalence data, particularly that using biological samples. Whilst there is evidence of increasing use of SCs throughout the world, in Saudi Arabia, there is currently no data regarding the use of products containing SCs among Saudi people. Several studies indicate that SCs may cause serious toxicity and impairment to health therefore it is important to understand the scale of use within society. A simple and sensitive method was developed for the simultaneous analysis of 10 parent SCs (JWH-018, JWH-073, JWH-250, JWH-200, AM-1248, UR-144, A-796260, AB-FUBINACA, 5F-AKB-48 and 5F-PB-22) in whole blood and 8 corresponding metabolites (JWH-018 4-OH pentyl, JWH-073 3-OH butyl, JWH-250 4-OH pentyl, AM-2201 4-OH pentyl, JWH-122 5-OH pentyl, JWH-210 5-OH pentyl, 5F-AKB-48 (N-4 OH pentyl), 5F-PB-22 3-carboxyindole)in urine using LLE and LC-MS/MS. The method was validated according to the standard practices for method validation in forensic toxicology (SWGTOX, May 2013). All analytes gave acceptable precision, linearity and recovery for analysing blood and urine samples. The method was applied to 1,496 biological samples, a mixture of whole blood and urine. Blood and/or urine samples were analysed from 114 patients presenting at Accident and Emergency in Glasgow Royal Infirmary, in spring 2014 and JuneDecember 2015. 5F-AKB-48, 5F-PB-22 and MDMB-CHMICA were detected in 9, 7 and 9 cases respectively. 904 urine samples from individuals admitted to/liberated from Scottish prisons over November 2013 were tested for the presence of SCs. 5F-AKB-48 (N-4 OH pentyl) was detected in 10 cases and 5F-PB-22 3-carboxyindole in 3 cases. Blood and urine samples from two post-mortem cases in Scotland with suspected ingestion of SCs were analysed. Both cases were confirmed positive for 5F-AKB-48. A total of 463 urine samples were collected from personnel who presented to the Security Forces Hospital in Ryiadh for workplace drug testing as a requirement for their job during July 2014. The results of the analysis found 2 samples to be positive for 5F-PB-22 3carboxyindole. A further study in Saudi Arabia using a questionnaire was carried out among 3 subpopulations: medical professionals, members of the public in and around smoking cafes and known drug users. With regards to general awareness of Spice products, 16%, 11% and 22% of those participants of medical professionals, members of the public in and around smoking cafes and known drug users, respectively, were aware of the existence of SCs or Spice products. The respondents had an overall average of 4.5% who had a friend who used these Spice products. It is clear from the results obtained in both blood and urine testing and surveys that SCs are being used in both Scotland and Saudi Arabia. The extent of their use is not clear and the data presented here is an initial look into their prevalence. Blood and urine findings suggest changing trends in SC use, moving away from JWH and AM SCs to the newer 5F-AKB-48, 5-F-PB-22 and MDMBCHMICA compounds worldwide. In both countries 5F-PB-22 was detected. These findings clarify how the SCs phenomenon is a worldwide problem and how the information of every country regarding what SCs are seized can help and is not specific for that country. The analytes included in the method were selected due to their apparent availability in both countries, however it is possible that some newer analytes have been used and these would not have been detected. For this reason it is important that methods for testing SCs are updated regularly and evolve with the ever-changing availability of these drugs worldwide. In addition, there is little published literature regarding the concentrations of these drugs found in blood and urine samples and this work goes some way towards understanding these.

Glutathione Transferases as Detoxification Agents: Structural and Functional Studies

Glutathione transferases (GSTs) are a diverse family of enzymes that catalyze the glutathione-dependent detoxification of toxic compounds. GSTs are responsible for the conjugation of the tripeptide glutathione (GSH) to a wide range of electrophilic substrates. These include industrial pollutants, drugs, genotoxic carcinogen metabolites, antibiotics, insecticides and herbicides. In light of applications in biomedicine and biotechnology as cellular detoxification agents, detailed structural and functional studies of GSTs are required. Plant tau class GSTs play crucial catalytic and non-catalytic roles in cellular xenobiotic detoxification process in agronomically important crops. The abundant existence of GSTs in Glycine max and their ability to provide resistance to abiotic and biotic stresses such as herbicide tolerance is of great interest in agriculture because they provide effective and suitable tools for selective weed control. Structural and catalytic studies on tau class GST isoenzymes from Glycine max (GmGSTU10-10, GmGSTU chimeric clone 14 (Sh14), and GmGSTU2-2) were performed. Crystal structures of GmGSTU10-10 in complex with glutathione sulfenic acid (GSOH) and Sh14 in complex with S-(p-nitrobenzyl)-glutathione (Nb-GSH) were determined by molecular replacement at 1.6 Å and 1.75 Å, respectively. Major structural variations that affect substrate recognition and catalytic mechanism were revealed in the upper part of helix H4 and helix H9 of GmGSTU10-10. Structural analysis of Sh14 showed that the Trp114Cys point mutation is responsible for the enhanced catalytic activity of the enzyme. Furthermore, two salt bridges that trigger an allosteric effect between the H-sites were identified at the dimer interface between Glu66 and Lys104. The 3D structure of GmGSTU2-2 was predicted using homology modeling. Structural and phylogenetic analysis suggested GmGSTU2-2 shares residues that are crucial for the catalytic activity of other tau class GSTs–Phe10, Trp11, Ser13, Arg20, Tyr30, Leu37, Lys40, Lys53, Ile54, Glu66 and Ser67. This indicates that the catalytic and ligand binding site in GmGSTU2-2 are well-conserved. Nevertheless, at the ligandin binding site a significant variation was observed. Tyr32 is replaced by Ser32 in GmGSTU2-2 and thismay affect the ligand recognition and binding properties of GmGSTU2-2. Moreover, docking studies revealed important amino acid residues in the hydrophobic binding site that can affect the substrate specificity of the enzyme. Phe10, Pro12, Phe15, Leu37, Phe107, Trp114, Trp163, Phe208, Ile212, and Phe216 could form the hydrophobic ligand binding site and bind fluorodifen. Additionally, side chains of Arg111 and Lys215 could stabilize the binding through hydrogen bonds with the –NO2 groups of fluorodifen. GST gene family from the pathogenic soil bacterium Agrobacterium tumefaciens C58 was characterized and eight GST-like proteins in A. tumefaciens (AtuGSTs) were identified. Phylogenetic analysis revealed that four members of AtuGSTs belong to a previously recognized bacterial beta GST class and one member to theta class. Nevertheless, three AtuGSTs do not belong to any previously known GST classes. The 3D structures of AtuGSTs were predicted using homology modeling. Comparative structural and sequence analysis of the AtuGSTs showed local sequence and structural characteristics between different GST isoenzymes and classes. Interactions at the G-site are conserved, however, significant variations were seen at the active site and the H5b helix at the C-terminal domain. H5b contributes to the formation of the hydrophobic ligand binding site and is responsible for recognition of the electrophilic moiety of the xenobiotic. It is noted that the position of H5b varies among models, thus providing different specificities. Moreover, AtuGSTs appear to form functional dimers through diverse modes. AtuGST1, AtuGST3, AtuGST4 and AtuGST8 use hydrophobic ‘lock–and–key’-like motifs whereas the dimer interface of AtuGST2, AtuGST5, AtuGST6 and AtuGST7 is dominated by polar interactions. These results suggested that AtuGSTs could be involved in a broad range of biological functions including stress tolerance and detoxification of toxic compounds.

Administrative justice and the control of bureaucratic decision-making: A study investigating how decision-makers in local authority education departments respond to the work of redress mechanisms

This socio-legal thesis has explored the factors responsible for explaining whether and how redress mechanisms control bureaucratic decision-making. The research considered the three principal institutions of administrative justice: courts, tribunals, and ombudsman schemes. The field setting was the local authority education area and the thesis examined bureaucratic decision-making about admissions to school, home-to-school transport, and Special Educational Needs (SEN). The thesis adopted a qualitative approach, using interviews and documentary research, within a multiple embedded case study design. The intellectual foundations of the research were inter-disciplinary, cutting across law, socio-legal studies, public administration, organization studies, and social policy. The thesis drew on these scholarly fields to explore the nature of bureaucratic decision-making, the extent to which it can be controlled and the way that learning occurs in bureaucracies and, finally, the extent to which redress mechanisms might exercise control. The concept of control was studied across all its dimensions – in relation both to ex post control in specific cases and the more challenging notion of ex ante or structuring control. The aim of the thesis was not to measure the prevalence of bureaucratic control by redress mechanisms, but to understand the factors that might explain its presence or absence in a particular area. The findings of the research have allowed for a number of analytical refinements and extensions to be made to existing theoretical and empirical understandings. 14 factors, along with 87 supporting propositions, have been set out with the aim of making empirically derived suggestions which can be followed up in future research. In terms of the thesis’ contribution to existing knowledge, its comparative focus and its emphasis on the broad notion of control offered the potential for new insights to be developed. Overall, the thesis claims to have made three contributions to the conceptual framework for understanding the exercise of control by redress mechanisms: it emphasizes the importance of ‘feedback’ in relation to the nature of the cases referred to redress mechanisms; it calls attention to the structure of bureaucratic decision-making as well as its normative character; and it discusses how the operational modes of redress mechanisms relate to their control functions.

Convenio de Colaboración entre la University of Victoria (Representada por el Department of Hispanic and Italian Studies), Victoria, Columbia Británica, Canadá, y la Universidad de Cuenca (Programa de Español para Extranjeros, Departamento de Idiomas), Cuenca, Ecuador

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Reproductive decisions of couples living with HIV in Malawi: What can we learn for future policy and research studies?

Background The rapid scale-up of free antiretroviral therapy has lead to decline in adult mortality at the population level and reduction of vertical transmission. Consequently, some couples living with HIV are maintaining their reproductive decisions; marrying and having children. This paper analyses policies and guidelines on HIV, AIDS and sexual and reproductive health in Malawi for content on marriage and childbearing for couples living with HIV. Methods A qualitative study using interpretive policy analysis approach was conducted from July to December 2010 in two phases. First, data on access to HIV, AIDS and sexual and reproductive health services were collected using in-depth interviews with twenty couples purposively sampled in matrilineal Chiradzulu and patrilineal Chikhwawa communities. Secondly, data were collected from Malawi policies and guidelines on HIV, AIDS and sexual and reproductive health. The documents were reviewed for content on marriage and childbearing for couples living with HIV. Data were analysed using framework approach for applied policy analysis. Results Four categories emerged from each phase. From the study, we extracted health workers attitudes, weak linkage between HIV, AIDS and sexual and reproductive health services, contradictory messages between media and the hospitals and lack of information as factors directly related to guidelines and policies. Analysis of guidelines and policies showed nonprescriptiveness on issues of HIV, AIDS and reproduction: they do not reflect the social cultural experiences of couples living with HIV. In addition, there is; lack of clinical guidelines, external influence on adoption of the policies and guidelines and weak linkages between HIV and AIDS and sexual and reproductive health services. Conclusion This synthesis along with more detailed findings which are reported in other published articles, provide a strong basis for updating the policies and development of easy-to-follow guidelines in order to effectively provide services to couples living with HIV in Malawi.

Surveillance, criminal law and sovereighty

Seeking better understanding of the relationship between criminal law and surveillance demands investigating the evolving nature of sovereignty in an era of transnational digital information flows. While territorial boundaries determine the limits of police investigative and surveillance powers under the criminal law, several recent United States (US) examples demonstrate how new forms of extraterritorial surveillance that enable police to access online communications by foreign citizens and digital information stored in offshore locations are authorized by US courts. This discussion outlines how the processes of mutual legal assistance that ordinarily govern the search, seizure and transfer of digital evidence from one jurisdiction to another are increasingly considered to undermine police efficiency, even though they protect the due process rights afforded to crime suspects under established principles of sovereignty (Palmer and Warren 2013).

First law and the force of water: law, water, entitlement

In this essay, the authors respond to several of the papers included in this special issue. First reflecting on the relation between waters, ‘First law’,1 and settler law, the authors then draw connections between some of the contributions to the issue. Water, the authors contend, is a productive site for thinking through the organs and processes of settler law, though such attention, they argue, also reveals how the ‘constitutional’ question of waters is occluded by the presence and dominance of settler law. The final section turns to Aotearoa/New Zealand as a negative example of this situation, one in which the constituting force of waters is nullified by the incorporation of indigenous politics within the processes and institutions of the settler legal order.

Combined nano- and macrotribology studies of titania lubrication using the oil-ionic liquid mixtures

The lubrication of titania surfaces using a series of ionic liquid (IL)-hexadecane mixtures has been probed using nanoscale atomic force microscopy (AFM) and macroscale ball-on-disk tribometer measurements. The IL investigated is trihexyl(tetradecyl)phosphonium bis(2,4,4-trimethylpentyl)phosphinate, which is miscible with hexadecane in all proportions. At both length scales, the pure IL is a much more effective lubricant than pure hexadecane. At low loads, which are comparable to common industrial applications, the pure IL reduces the friction by 80% compared to pure hexadecane; while the IL-hexadecane mixtures lubricate the titania surface as effectively as the pure IL and wear decreases with increasing IL concentration. At high test loads the adsorbed ion boundary layer is displaced leading to surface contact and high friction, and wear is pronounced for all IL concentrations. Nonetheless, the IL performs better than a traditional zinc-dialkyl-dithophosphate (ZDDP) antiwear additive at the same concentration.

Quarantine facilities and legal issues of the use of biocontrol agents in Brazil.

The objective of this work was to address the classical biological control of pests in Brazil, regarding procedures to import and export native biological material. A brief introduction will be given on the current legal issues on the use of biocontrol agents, as well as some considerations on the existing quarantine pests and actions already carried out in the country. The safety in the introduction of exotic organisms is important for Brazilian phytosanitary defense and for a higher adoption of classical biocontrol, making it available for integrated pest management (IPM). Legal and normative aspects establish the procedures that must to be adopted, not only to protect bioprospecting and native organisms, but also to minimize risks to the national genetic patrimony associated with the introduction of exotic organisms. Furthermore, the import/export procedures adopted for vegetal and useful organisms for pest biological control and for other genetic material must be subjected to phytosanitary measures performed in government?certified quarantine facilities and diagnostic laboratories. Finally, the quarantine activities listed here are strategic for safeguarding the country from potential problems arising from border transit of living organisms.