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OBJECTIVE: To assess a technique for laparoscopic collection of serial full-thickness small intestinal biopsy specimens in horses. ANIMALS:13 healthy adult horses. PROCEDURES: In the ex vivo portion of the study, sections of duodenum and jejunum obtained from 6 horses immediately after euthanasia were divided into 3 segments. Each segment was randomly assigned to the control group, the double-layer hand-sewn closure group, or the endoscopic linear stapler (ELS) group. Bursting strength and bursting wall tension were measured and compared among groups; luminal diameter reduction at the biopsy site was compared between the biopsy groups. In the in vivo portion of the study, serial full-thickness small intestinal biopsy specimens were laparoscopically collected with an ELS from the descending duodenum and distal portion of the jejunum at monthly intervals in 7 sedated, standing horses. Biopsy specimens were evaluated for suitability for histologic examination. RESULTS: Mean bursting strength and bursting wall tension were significantly lower in the ELS group than in the hand-sewn and control groups in both the duodenal and jejunal segments. Use of the hand-sewn closure technique at the biopsy site reduced luminal diameter significantly more than use of the stapling technique. In the in vivo part of the study, all 52 biopsy specimens collected during 26 laparoscopic procedures were suitable for histologic examination and no clinically important perioperative complications developed. CONCLUSIONS AND CLINICAL RELEVANCE: Laparoscopic collection of serial full-thickness small intestinal biopsy specimens with a 45-mm ELS may be an effective and safe technique for use in healthy adult experimental horses.
Bracamonte JLBoure LPGeor RJRunciman JRNykamp SGCruz AMTeeter MGWaterfall HL
Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada.
OBJECTIVE: To assess the sedative and cardiopulmonary effects of medetomidine and xylazine and their reversal with atipamezole in calves. ANIMALS: 25 calves. PROCEDURES: A 2-phase (7-day interval) study was performed. Sedative characteristics (phase I) and cardiopulmonary effects (phase II) of medetomidine hydrochloride and xylazine hydrochloride administration followed by atipamezole hydrochloride administration were evaluated. In both phases, calves were randomly allocated to receive 1 of 4 treatments IV: medetomidine (0.03 mg/kg) followed by atipamezole (0.1 mg/kg; n = 6), xylazine (0.3 mg/kg) followed by atipamezole (0.04 mg/kg; 7), medetomidine (0.03 mg/kg) followed by saline (0.9% NaCl; 6) solution (10 mL), and xylazine (0.3 mg/kg) followed by saline solution (10 mL; 6). Atipamezole or saline solution was administered 20 minutes after the first injection. Cardiopulmonary variables were recorded at intervals for 35 minutes after medetomidine or xylazine administration. RESULTS: At the doses evaluated, xylazine and medetomidine induced a similar degree of sedation in calves; however, the duration of medetomidine-associated sedation was longer. Compared with pretreatment values, heart rate, cardiac index, and PaO(2) decreased, whereas central venous pressure, PaCO(2), and pulmonary artery pressures increased with medetomidine or xylazine. Systemic arterial blood pressures and vascular resistance increased with medetomidine and decreased with xylazine. Atipamezole reversed the sedative and most of the cardiopulmonary effects of both drugs. CONCLUSIONS AND CLINICAL RELEVANCE: At these doses, xylazine and medetomidine induced similar degrees of sedation and cardiopulmonary depression in calves, although medetomidine administration resulted in increases in systemic arterial blood pressures. Atipamezole effectively reversed medetomidine- and xylazine-associated sedative and cardiopulmonary effects in calves.
Rioja EKerr CLEnouri SSMcDonell WN
Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada.
Aims This study was designed to develop and evaluate a self-report measure of gambling motives. Participants A community-recruited sample of 193 gamblers (70% male; mean age = 35.5 years) were selected to fill two groups according to scores on the South Oaks Gambling Screen: probable pathological gamblers (PPG; n = 154) and non-pathological gamblers (NPG; n = 39). Measures Participants completed a novel 15-item measure of gambling motives called the Gambling Motives Questionnaire (GMQ), which was modeled after the original Drinking Motives Questionnaire, as well as a variety of gambling behavior and problem criterion measures. Results An exploratory principal components analysis revealed three intercorrelated factors tapping enhancement (ENH), coping (COP), and social (SOC) motives, respectively. Each GMQ subscale showed good internal consistency (alphas > 0.80). The PPG group scored higher on all three scales than the NPG group, with larger differences for ENH and COP. In line with the clinical literature, PPG women scored higher than PPG men on the COP subscale but also, unexpectedly, on the SOC subscale. In concurrent validity analyses, ENH consistently predicted greater gambling behavior, and COP and ENH consistently predicted more severe gambling problems. With gambling behavior levels controlled, only COP remained a significant predictor of gambling problem severity. Finally, gender interacted with gambling motives in predicting gambling problem severity: COP predicted gambling problems more strongly in women, whereas ENH predicted gambling problems more strongly in men. Conclusions The GMQ appears to be a promising tool for both research and clinical applications with problem gamblers.
Stewart,SH Zack,M
Department of Psychiatry, Dalhousie University, Halifax, NS, Canada.
Objective-To determine the effects of dexamethasone treatment on selected components of insulin signaling and glucose metabolism in skeletal muscle obtained from horses before and after administration of a euglycemic-hyperinsulinemic clamp (EHC). Animals-6 adult Standardbreds. Procedures-In a balanced crossover study, horses received either dexamethasone (0.08 mg/kg, IV, q 48 h) or an equivalent volume of saline (0.9% NaCl) solution, IV, for 21 days. A 2-hour EHC was administered for measurement of insulin sensitivity 1 day after treatment. Muscle biopsy specimens obtained before and after the EHC were analyzed for glucose transporter 4, protein kinase B (PKB), glycogen synthase kinase (GSK)-3alpha/beta protein abundance and phosphorylation state (PKB Ser(473) and GSK-3alpha/beta Ser(21/9)), glycogen synthase and hexokinase enzyme activities, and muscle glycogen concentration. Results-Dexamethasone treatment resulted in resting hyperinsulinemia and a significant decrease (70%) in glucose infusion rate during the EHC. In the dexamethasone group, increased hexokinase activity, abrogation of the insulin-stimulated increase in glycogen synthase fractional velocity, and decreased phosphorylation of GSK-3alpha Ser(21) and GSK-3B Ser(9) were detected, but there was no effect of dexamethasone treatment on glucose transporter 4 content and glycogen concentration or on PKB abundance and phosphorylation state. Conclusions and Clinical Relevance-In horses, 21 days of dexamethasone treatment resulted in substantial insulin resistance and impaired GSK-3 phosphorylation in skeletal muscle, which may have contributed to the decreased glycogen synthase activity seen after insulin stimulation.
Tiley HA Geor RJ McCutcheon LJ
Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada.
The development of a safe and efficacious drug involves a balance between bioavailability, toxicity and disposition within the body. If the drug is hydrophobic or acid labile, oral administration may lead to poor systemic exposure, necessitating a parenteral treatment regime. Amphotericin B (AmpB) is one example of a well established, highly efficacious drug that has a 50 year history of intravenous therapy. AmpB formulated as a micellar dispersion (Fungizone?; FZ) for IV use, remains one of the most effective agents in the treatment of systemic fungal infections, yet no oral formulations are currently commercially available. Recently, our laboratory has developed new oral lipid-based AmpB formulations with enhanced gastrointestinal (GI) tract absorption and antifungal activity with minimum renal toxicity. This review article will discuss these findings and present data to support two potential mechanisms for the enhanced GI tract absorption of AmpB when formulated in this oral lipid-based delivery system, namely an increase in lymphatic drug transport and a decrease in pre-systemic transporter-mediated drug efflux.
Kristina Sachs-Barrablea Stephen D. Leea Ellen K. Wasana Sheila J. Thorntona Kishor M. WasanaEmail:kwasan@interchange.ubc.ca
[a]Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada V6T 1Z3;[b]School of Health Sciences, British Columbia Institute of Technology, Burnaby BC, Canada
AIMS: Following an ecological model to specify risks for impaired driving, we assessed the effects of youth attitudes about substance use and their experiences of riding in cars with adults and peers who drove after drinking alcohol or smoking cannabis on the youths’ own driving after drinking or using cannabis. DESIGN AND METHODS: Participants were 2594 students in grades 10 and 12 (mean age 16 years and 2 months; 50% girls) from public high schools in urban (994) and rural communities (1600) on Vancouver Island in British Columbia, Canada; 1192 of these were new drivers with restricted licenses. Self-report data were collected in anonymous questionnaires. Regression analyses were used to assess the independent and interacting effects of youth attitudes about substance use and their experiences of riding in cars with adults or peers who drove after drinking alcohol or smoking cannabis on youth driving. FINDINGS: Youth driving risk behaviors were associated independently with their own high-risk attitudes and experiences riding with peers who drink alcohol or use cannabis and drive. However, risks were highest for the youth who also report more frequent experiences of riding with adults who drink alcohol or use cannabis and drive. CONCLUSIONS: Prevention efforts should be expanded to include the adults and peers who are role models for new drivers and to increase youths’ awareness of their own responsibilities for their personal safety as passengers.
Leadbeater,BJ Foran,K Grove-White,A
Centre for Youth and Society, University of Victoria, Victoria, British Columbia, Canada. bleadbea@uvic.ca
The development of a safe and efficacious drug involves a balance between bioavailability, toxicity and disposition within the body. If the drug is hydrophobic or acid labile, oral administration may lead to poor systemic exposure, necessitating a parenteral treatment regime. Amphotericin B (AmpB) is one example of a well established, highly efficacious drug that has a 50 year history of intravenous therapy. AmpB formulated as a micellar dispersion (Fungizone?; FZ) for IV use, remains one of the most effective agents in the treatment of systemic fungal infections, yet no oral formulations are currently commercially available. Recently, our laboratory has developed new oral lipid-based AmpB formulations with enhanced gastrointestinal (GI) tract absorption and antifungal activity with minimum renal toxicity. This review article will discuss these findings and present data to support two potential mechanisms for the enhanced GI tract absorption of AmpB when formulated in this oral lipid-based delivery system, namely an increase in lymphatic drug transport and a decrease in pre-systemic transporter-mediated drug efflux.
Kristina Sachs-Barrablea Stephen D. Leea Ellen K. Wasana Sheila J. Thorntona Kishor M. WasanaEmail:kwasan@interchange.ubc.ca
[a]Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada V6T 1Z3;[b]School of Health Sciences, British Columbia Institute of Technology, Burnaby BC, Canada
AIMS: Previous studies have shown inconsistent findings with regard to the association between amount of spending money and adolescent smoking. Drinking alcohol may be a mediator of the association between spending money and adolescent smoking. However, no studies have examined this potential role. The objective of this study was to investigate the association between amount of spending money and adolescent smoking and the potential mediation role of alcohol use in this association. DESIGN: The 2003 Ontario Student Drug Use Survey of students in grades 7-12. MEASUREMENTS: Multivariable logistic, probit and linear regression models were used to investigate the association between amount of spending money and smoking, and the contribution of drinking alcoholic beverages to this relationship. FINDINGS: Spending money was associated positively with experimental smoking, current smoking and daily consumption of cigarettes (P < 0.01). The analysis adjusted for confounders showed that students with spending money > or =Dollars 20/week were significantly more likely to be experimental smokers, students with > or =Dollars 30/week were significantly more likely to be current smokers and students with > or =Dollars 60/week smoked significantly more cigarettes/day (P < or 0.05), compared to students with
Zhang,B Cartmill,C Ferrence,R
Ontario Tobacco Research Unit, University of Toronto, Toronto, ON, Canada. bo_zhang@camh.net
Targeted delivery of drug molecules to organs or special sites is one of the most challenging research areas in pharmaceutical sciences. By developing colloidal delivery systems such as liposomes, micelles and nanoparticles a new frontier was opened for improving drug delivery. Nanoparticles with their special characteristics such as small particle size, large surface area and the capability of changing their surface properties have numerous advantages compared with other delivery systems. Targeted nanoparticle delivery to the lungs is an emerging area of interest. This article reviews research performed over the last decades on the application of nanoparticles administered via different routes of administration for treatment or diagnostic purposes. Nanotoxicological aspects of pulmonary delivery are also discussed.
Shirzad Azarmia Wilson H. Roac Raimar Lbenberga Email:rloebenberg@pharmacy.ualberta.ca
[a]Faculty of Pharmacy; Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada;[b]Research Centre for Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran;[c]Department of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, Canada
Noninvasive, transient, and local image-guided blood-brain barrier disruption (BBBD) has been demonstrated with focused ultrasound exposure in animal models. Most studies have combined low pressure amplitude and low time average acoustic power burst sonications with intravascular injection of pre-formed micro-bubbles to produce BBBD without damage to the neurons. The BBB has been shown to be healed within a few hours after the exposure. The combination of focused ultrasound beams with MR image guidance allows precise anatomical targeting as demonstrated by the delivery of several marker molecules in different animal models. This method may in the future have a significant impact on the diagnosis and treatment of central nervous system (CNS) disorders. Most notably, the delivery of the chemotherapy agents (liposomal Doxorubicin and Herceptin) has been shown in a rat model.
Hynynen,K
Department of Medical Biophysics, University of Toronto, Sunnybrook Health Sciences Centre, 2075 Bayview Ave, Toronto, ON, Canada. khynynen@sri.utoronto.ca