Mephedrone pharmacokinetics after intravenous and oral administration in rats: relation to pharmacodynamics

Rationale Mephedrone (4-methylmethcathinone) is a still poorly known drug of abuse, alternative to ecstasy or cocaine. Objective The major aims were to investigate the pharmacokineticsa and locomotor activity of mephedrone in rats and provide a pharmacokinetic/pharmacodynamic model. Methods Mephedrone was administered to male Sprague-Dawley rats intravenously (10 mg/kg) and orally (30 and 60 mg/kg). Plasma concentrations and metabolites were characterized using LC/MS and LC-MS/MS fragmentation patterns. Locomotor activity was monitored for 180-240 min. Results Mephedrone plasma concentrations after i.v. administration fit a two-compartment model (α=10.23 h−1, β=1.86 h−1). After oral administration, peak mephedrone concentrations were achieved between 0.5 and 1 h and declined to undetectable levels at 9 h. The absolute bioavailability of mephedrone was about 10 % and the percentage of mephedrone protein binding was 21.59±3.67%. We have identified five phase I metabolites in rat blood after oral administration. The relationship between brain levels and free plasma concentration was 1.85±0.08. Mephedrone induced a dose-dependent increase in locomotor activity, which lasted up to 2 h. The pharmacokinetic-pharmacodynamic model successfully describes the relationship between mephedrone plasma concentrations and its psychostimulant effect. Conclusions We suggest a very important first-pass effect for mephedrone after oral administration and an easy access to the central nervous system. The model described might be useful in the estimation and prediction of the onset, magnitude,and time course of mephedrone pharmacodynamics as well as to design new animal models of mephedrone addiction and toxicity.

CRM and higher education : developing a monitoring system to improve relationships in e-learning environments

Peer-reviewed

Trypanosoma cruzi infection and/or administration of the nonsteroidal anti-inflammatory nimesulide increase the number of colonic crypts overexpressing metallothioneins in rat colon carcinogenesis

Trypanosoma cruzi infection and nonsteroidal anti-inflammatory drugs inhibit colorectal carcinogenesis by mechanisms not completely known and metallothionein proteins (MTs) may be involved in this process. Sixty-six male Wistar rats weighing 90 to 120 g were randomly divided into seven groups (GI to GVII). GI, GII and GIII animals were subcutaneously infected with 200,000 trypomastigote forms of the Y strain of T. cruzi. After 8 weeks, GI, GII, GIV, and GVI were injected with one weekly subcutaneous dose of 12 mg/kg dimethylhydrazine for 4 weeks. In sequence, GI, GIV and GV were treated with nimesulide (10 mg/kg per dose, five times per week for 8 weeks). Groups I, III, IV, and VI had 12 animals, and each of the other groups had 6 animals. All the animals were euthanized 8 weeks after the last dimethylhydrazine injection. The colons were fixed and processed for MT immunohistochemistry. The index of MT-overexpressing colonic crypts (MTEC) was estimated as the percentage of MT-stained crypts in relation to the total number of crypts scored. Five hundred crypts per animal were scored. Data were analyzed by the Kruskal-Wallis test followed by the Dunn test. There was an increase in MTEC index in the groups either infected with T. cruzi or treated with nimesulide or both infected and treated when compared to control (401, 809, and 1011%, respectively). We suggest that the increased formation of MTEC may be related to the protection against carcinogenesis provided both by T. cruzi infection and nimesulide.

Effects of chronic corticosterone and imipramine administration on panic and anxiety-related responses

It is known that chronic high levels of corticosterone (CORT) enhance aversive responses such as avoidance and contextual freezing. In contrast, chronic CORT does not alter defensive behavior induced by the exposure to a predator odor. Since different defense-related responses have been associated with specific anxiety disorders found in clinical settings, the observation that chronic CORT alters some defensive behaviors but not others might be relevant to the understanding of the neurobiology of anxiety. In the present study, we investigated the effects of chronic CORT administration (through surgical implantation of a 21-day release 200 mg pellet) on avoidance acquisition and escape expression by male Wistar rats (200 g in weight at the beginning of the experiments, N = 6-10/group) tested in the elevated T-maze (ETM). These defensive behaviors have been associated with generalized anxiety and panic disorder, respectively. Since the tricyclic antidepressant imipramine is successfully used to treat both conditions, the effects of combined treatment with chronic imipramine (15 mg, ip) and CORT were also investigated. Results showed that chronic CORT facilitated avoidance performance, an anxiogenic-like effect (P < 0.05), without changing escape responses. Imipramine significantly reversed the anxiogenic effect of CORT (P < 0.05), although the drug did not exhibit anxiolytic effects by itself. Confirming previous observations, imipramine inhibited escape responses, a panicolytic-like effect. Unlike chronic CORT, imipramine also decreased locomotor activity in an open field. These data suggest that chronic CORT specifically altered ETM avoidance, a fact that should be relevant to a better understanding of the physiopathology of generalized anxiety and panic disorder.

An examination of the mediation process as it is used to resolve sexual harassment complaints in Canadian universities /

The ways in which the process of mediation affected those involved in the resolution of sexual harassment complaints in Canadian universities were explored. Questionnaires were sent to forty- six Canadian universities and interviews were conducted with fifteen advisors. An analysis of the twenty- two questionnaires returned indicated that mediation was utilized in 11% of the sexual harassment complaints and effected a successful resolution in 67% of these. Both complainants and those con^lained against were reported to have spoken more favourably than unfavourably about the process and outcome of mediation. Questionnaire respondents in general found mediation a slightly less than satisfactory method of complaint resolution. Those respondents who had successfully used mediation; however, describe its usefulness within a university context.

Guerrillas in the mi(d)st: a study of discreet dissension amoung administrators in academe /

This qualitative study examines the phenomenon of discreet dissension in the administration of academe through literature review and the focused reflections of retired, senior administrators of postsecondary institutions in Ontario. Discretionary decision making is a large component of senior administrative positions. At times, senior administrators use their discretion to engage in institutionally endorsed behaviour to fulfill institutionally sanctioned objectives. At other times, senior administrators use their discretion to engage in dissenting courses of action, contrary to the prescribed and codified policies, procedures, and norms of the institution in order to achieve institutionally endorsed objectives and/or to achieve objectives congruent with individual values. Discreet dissension emerges as an administrative activity for further investigation, enhancing the understanding of the art of administration.

An exploration of transformation theory and the western tradition: a critical evaluation of a graduate studies class

This qualitative study is an exploration of transformation theory, the Western tradition, and a critical evaluation of a graduate studies class at a university. It is an exploration of assumptions that are embedded in experience, that influence the experience and provide meaning about the experience. An attempt has been made to identify assumptions that are embedded in Western experience and connect them with assumptions that shape the graduate class experience. The focus is on assumptions that facilitate and impede large group discussions. Jungian psychology of personality type and archetype and developmental psychology is used to analyze the group experience. The pragmatic problem solving model, developed by Knoop, is used to guide thinking about the Western tradition. It is used to guide the analysis, synthesis and writing of the experience of the graduate studies class members. A search through Western history, philosophy. and science revealed assumptions about the nature of truth, reality, and the self. Assumptions embedded in Western thinking about the subject-object relationship, unity and diversity are made explicit. An attempt is made to identify Western tradition assumptions underlying transformation theory. The critical evaluation of the graduate studies class experience focuses upon issues associated with group process, self-directed learning, the educator-learner transaction and the definition of adult education. The advantages of making implicit assumptions explicit is explored.

Partnership, politics and public administration: a case study of the Ontario Ministry of Natural Resources

Efforts to reform the public sector reflect the social, political and economic environment within which government must function. The recent demands by the public for more consensual decision-making, as well as more efficient, effective and responsive public service, have resulted in a number of reform initiatives, including an emphasis on partnership development. The purpose of this thesis is to examine partnership arrangements within the public sector. Specifically, the thesis will assess the value of partnerships and their impact on government by examining six partnership arrangements involving the Ontario Ministry of Natural Resources (OMNR). The OMNR, having recently been awarded the 1992 Institute of Public Administration of Canada Award for Innovative Management, on the theme of partnership development, is being lauded as an example for other government agencies considering similar alliances. The thesis begins by introducing the concept and practice of partnership within the public sector in general and the OMNR specifically. Descriptive analysis of six OMNR partnerships is provided and a number of criteria are used to determine the success of each of these arrangements. Special attention is paid to the political implications of partnerships and to those attributes which appear to contribute to the successful establishment and iii maintenance of partnership arrangements. The conclusion is drawn that partnerships provide the government with an opportunity to address public demands for greater involvement in decision-making while accommodating government's limited financial resources. However, few truly collaborative partnerships exist within the public sector. There are also significant political implications associated with partnerships which must be dealt with both at the political and bureaucratic levels of government. Lastly, it is argued that while partnerships within the OMNR are experiencing some difficulties, they constitute a genuine attempt to broaden the base of decision-making and to incorporate the concerns of stakeholders into resource management.

The association of faculty's teaching philosophy and teaching behaviour, and critical thinking and self- direction in learning

The intent in this study was to investigate in what ways teachers· beliefs about education and teaching are expressed in the specific teaching behaviours they employ, and whether teaching behaviours, as perceived by their students, are correlated with students· critical thinking and self-directed learning. To this end the relationships studied were: among faCUlty members· philosophy of teaching, locus of control orientation, psychological type, and observed teaching behaviour; and among students· psychological type, perceptions of teaching behaviour, self-directed learning readiness, and critical thinking. The overall purpose of the study was to investigate whether the implicit goals of higher education, critical thinking and self-direction, were actually accounted for in the university classroom. The research was set within the context of path-goal theory, adapted from the leadership literature. Within this framework, Mezirow·s work on transformative learning, including the influences of Habermas· writings, was integrated to develop a theoretical perspective upon which to base the research methodology. Both qualitative and quantitative methodologies were incorporated. Four faCUlty and a total of 142 students participated in the study. Philosophy of teaching was described through faCUlty interviews and completion of a repertory grid. Faculty completed a descriptive locus of control scale, and a psychological type test. Observations of their teaching behaviour were conducted. Students completed a Teaching Behaviour Assessment Scale, the Self-Directed Learning Readiness Scale, a psychological type test, and the Watson-Glaser Critical Thinking Appraisal. A small sample of students were interviewed. Follow-up discussions with faculty were used to validate the interview, observation, teaching behaviour, and repertory grid data. Results indicated that some discrepancies existed between faculty's espoused philosophy of teaching and their observed teaching behaviour. Instructors' teaching behaviour, however, was a function of their personal theory of practice. Relationships were found between perceived teaching behaviour and students· self-directed learning and critical thinking, but these varied across situations, as would be predicted from path-goal theory. Psychological type of students and instructor also accounted for some of the variability in the relationships studied. Student psychological type could be shown as a partial predictor of self-directed learning readiness. The results were discussed in terms of theory development and implications for further research and practice.

An Exploration Into Doctoral Students' Sense of Community and its Influence on the Formation of Informal Mentoring Relationships

This exploratory mixed method research project was designed to investigate an area of doctoral education that has received little attention in the past. This research focused specifically on the non-intellectual, hoped-for by-products of doctoral education; the dynamic processes of developing and maintaining both a sense of community and informal mentoring relationships. The design of the study captured the experiences of doctoral students and alumni at various time periods in the doctoral program. Participants represented a diverse group of students with differences in professional and academic backgrounds and life stages. A pilot study for this research suggested that the presence of a sense of community and informal mentoring may provide the necessary relationships to support this diversity. The primary question at the forefront of this study was: Do doctoral students feel connected to one another? Five subquestions were developed to address this research topic: Does a sense of community already exist and flourish in doctoral education? Are the programs and resources of the doctoral program organized to nurture the creation and maintenance of a sense of community? Is a sense of community a foundational element in the formation of naturally occurring relationships among doctoral students? What educational and socio-emotional benefits are associated with informal mentoring relationships during the doctoral experience? and Do doctoral students perceive a change in their development as stewards of their discipline over time? The principal methods used to investigate these research questions combined both quantitative and qualitative techniques in a concurrent time sequence. The quantitative portion of the study involved a questionnaire, while the qualitative portion involved two approaches; face-to-face interviews and an open-ended question at the end of the questionnaire. Findings from the study indicated that the presence of both sense of community and informal mentoring enhance the overall quality of doctoral education. Program elements that enhanced or hindered connection between students were identified. Both the dynamics and the emotional, social, and academic benefits of informal mentoring were elucidated. Over time participants perceived changes in their development of the qualities assqciated with stewardship. This study brought the "hoped-for by-products" associated with doctoral education from the background shadows to an illuminated position at the forefront of inquiry.

The perfect space: classroom environments and learning outcomes

Presentation at the Ontario Library Association Super Conference, January 28-21, 2015, Toronto, ON.

Rudimentary economics for schools and colleges

UANL