The North American Opiate Medication Initiative (NAOMI): Profile of Participants in North America’s First Trial of Heroin-Assisted Treatment

The North American Opiate Medication Initiative (NAOMI) is a randomized controlled trial evaluating the feasibility and effectiveness of heroin-assisted treatment (HAT) in the Canadian context. Our objective is to analyze the profile of the NAOMI participant cohort in the context of illicit opioid use in Canada and to evaluate its comparability with patient profiles of European HAT studies. Recruitment began in February 2005 and ended in March 2007. Inclusion criteria included opioid dependence, 5 or more years of opioid use, regular opioid injection, and at least two previous opiate addiction treatment attempts. Standardized assessment instruments such as the European Addiction Severity Index and the Maudsley Addiction Profile were employed. A total of 251 individuals were randomized from Vancouver, BC (192, 76.5%), and Montreal, Quebec (59, 23.5%); 38.5% were female, the mean age was 39.7 years (SD:8.6), and participants had injected drugs for 16.5 years (SD:9.9), on average. In the prior month, heroin was used a mean of 26.5 days (SD:7.4) and cocaine 16 days (SD;12.6). Vancouver had significantly more patients residing in unstable housing (88.5 vs. 22%; p < 0.001) and higher use of smoked crack cocaine (16.9 days vs. 2.3 days in the prior month; p < 0.001), while a significantly higher proportion of Montreal participants reported needle sharing in the prior 6 months (25% vs. 3.7%; p < 0.001). In many respects, the patient cohort was similar to the European trials; however, NAOMI had a higher proportion of female participants and participants residing in unstable housing. This study suggests that the NAOMI study successfully recruited participants with a profile indicated for HAT. It also raises concern about the high levels of crack cocaine use and social marginalization. Oviedo-Joekes, Marsh, Anis, and Schechter are with the School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada; Oviedo-Joekes, Nosyk, Chettiar, Marsh, Krausz, Anis, and Schechter are with the Centre for Health Evaluation and Outcome Sciences, Providence Health Care, Vancouver, BC, Canada; Brissette and Schneeberger are with the Centre de recherche du l’Université de Montréal, Montreal, QC, Canada; Marsh and Krausz are with the Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada; Marsh is with the Vancouver Coastal Health, Vancouver, BC, Canada; Marsh is with the Centre for Addiction Research British Columbia, Vancouver, BC, Canada.     

Cisatracurium in a myasthénic patient undergoing thymectomy

PURPOSE: The report investigates cisatracurium neuromuscular block in a myasthenic patient undergoing thymectomy. CLINICAL FEATURES: A myasthenic patient (Osserman II B) was prepared preoperatively with 240 mg x day(-1) pyridostigmine. The neuromuscular block produced by 0.05 mg x kg(-1) cisatracurium was monitored by Datex electromyography. The electromyographic response was compared with that in a control group of five non-myasthenic patients. In the myasthenic patient, cisatracurium resulted in a rapid onset of complete (97-98%) neuromuscular block, while a slow onset of partial (80-90%) block was achieved in the control group. Also, administration of 0.05 mg x kg(-1) neostigmine at the end of surgery reversed the neuromuscular block of cisatracurium in the non-myasthenic patients, but did not change the rate of spontaneous recovery in the myasthenic patient. CONCLUSION: The myasthenic patient is sensitive to cisatracurium, as evidenced by a more rapid onset and more marked neuromuscular block compared with the control non-myasthenic patients. This may be attributed to the decreased number of functional endplate acetylcholine receptors in the myasthenic patient, with a consequent decrease of the safety margin of neuromuscular transmission. Also, in contrast with the control group, the rate of recovery from neuromuscular block in the myasthenic patient was not enhanced by neostigmine at the end of surgery. This may be attributed to the prior inhibition of acetylcholinesterase by the preoperative pyridostigmine, as well as by possible desensitization of the cholinergic receptors secondary to prolonged pyridostigmine therapy.     

[<Superscript>18</Superscript>F]FDG PET Neuroimaging Predicts Pentylenetetrazole (PTZ) Kindling Outcome in Rats

Purpose

Epileptogenesis, i.e., development of epilepsy, involves a number of processes that alter the brain function in the way that triggers spontaneous seizures. Kindling is one of the most used animal models of temporal lobe epilepsy (TLE) and epileptogenesis, although chemical kindling suffers from high inter-assay success unpredictability. This study was aimed to analyze the eventual regional brain metabolic changes during epileptogenesis in the pentylenetetrazole (PTZ) kindling model in order to obtain a predictive kindling outcome parameter.

Procedures

In vivo longitudinal positron emission tomography (PET) scans with 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG) along the PTZ kindling protocol (35 mg/kg intraperitoneally (i.p.), 18 sessions) in adult male rats were performed in order to evaluate the regional brain metabolism.

Results

The half of the PTZ-injected rats reached the kindled state. In addition, a significant decrease of [¹⁸F]FDG uptake at the end of the protocol in most of the brain structures of kindled animals was found, reflecting the characteristic epilepsy-associated hypometabolism. However, PTZ-injected animals but not reaching the kindled state did not show this widespread brain hypometabolism. Retrospective analysis of the data revealed that hippocampal [¹⁸F]FDG uptake normalized to pons turned out to be a predictive index of the kindling outcome. Thus, a 19.06 % reduction (p?=?0.008) of the above parameter was found in positively kindled rats compared to non-kindled ones just after the fifth PTZ session.

Conclusion

Non-invasive PET neuroimaging was a useful tool for discerning epileptogenesis progression in this animal model. Particularly, the [¹⁸F]FDG uptake of the hippocampus proved to be an early predictive parameter to differentiate resistant and non-resistant animals to the PTZ kindling.

     

Development and Characterization of a Nonelectronic Versatile Oxygenating Perfusion System for Tissue Preservation

Annals of Biomedical Engineering - Oxygenated machine perfusion of human organs has been shown to improve both preservation quality and time duration when compared to the current gold standard:...     

Two 2-Hydroxy-3-Alkyl-1,4-Naphthoquinones with In Vitro and In Vivo Activities against Toxoplasma gondii

Two 3-alkyl-substituted 2-hydroxy-1,4-naphthoquinones, NSC 113452 (NSC52) and NSC 113455 (NSC55), were evaluated for activity against Toxoplasma gondii in vitro and in murine models of acute toxoplasmosis. In vitro, both NSC52 and NSC55 significantly inhibited intracellular replication of T. gondii. In vivo, each compound was examined alone and in combination with other drugs currently used for treatment of human toxoplasmosis. Although none of the compounds protected mice against death when administered orally, both were significantly protective when administered intraperitoneally. In addition, a significant increase in survival was observed when suboptimal doses of each compound were used in combination with suboptimal doses of pyrimethamine or sulfadiazine. These results indicate that combinations of NSC52 or NSC55 with pyrimethamine or sulfadiazine have promising activity against T. gondii.     

Characterization of bioactive compounds and ameliorative effects of Ceratonia siliqua leaf extract against CCl4 induced hepatic oxidative damage and renal failure in rats

Ceratonia siliqua is a typical Mediterranean plant, mainly used in food and Tunisian traditional folk medicine. Among the tested extracts, the ethyl acetate fraction (EACs) exhibited the highest total phenolic and flavonoids content. The antioxidant activity in vitro systems showed a more significant potent free radical scavenging activity of this extract than other analysis fractions. The HPLC finger print of EACs active extract showed the presence of six phenolic compounds. The in vivo results showed that oral administration of CCl₄ enhanced levels of hepatic and renal markers (ALT, AST, ALP, LDH, γ-GT, urea and creatinine) in the serum of experimental animals. It also increased the oxidative stress markers resulting in increased levels of the lipid peroxidation with a concomitant decrease in the levels of enzymatic antioxidants (SOD, CAT, GPx) in both liver and kidney. The pre-treatment of experimental rats with 250 mg/kg (BW) of the EACs, by intraperitoneal injection for 8 days, prevented CCl₄ induced disorders in the levels of hepatic and kidney markers. The biochemical changes were in accordance with histopathological observations suggesting a marked hepatoprotective and nephroprotective effect of the EACs extract.     

Synthesis of 4-hydroxycoumarin heteroarylhybrids as potential antimicrobial agents

A new series of 4-hydroxycoumarin derivatives 3a-d was synthesized by the reaction of 3-bromo-4-hydroxy coumarin 1 with various heteroaldehydes 2a-d in good yields. The synthesized compounds were characterized on the basis of their elemental and spectral (IR, (1)H-NMR and mass spectrometry) analysis. All target compounds were evaluated for their in-vitro antimicrobial activity against Streptococcus pyogenes, methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumonia, and Escherichia coli bacterial strains and fungal cultures of Candida albicans, Aspergillus fumigatus, Trichophyton mentagrophytes, and Penicillium marneffei by disk diffusion assay with slight modifications. The minimum inhibitory concentration (MIC) was determined for the test compounds as well as for reference standards. Among the tested compounds, 3a has shown the most potent antibacterial as well as antifungal activities.