Addiction research centres and the nurturing of creativity: the Department of Alcohol, Drugs and Addiction at the National Institute for Health and Welfare in Finland: diverse problems, diverse perspectives

The Department of Alcohol, Drugs and Addiction started operations on 1 January 2009, when the National Institute of Public Health (KTL) and the National Research and Development Centre for Welfare and Health (STAKES) were merged. The newly formed institute, called the National Institute for Health and Welfare (THL), operates under the Finnish Ministry of Social Affairs and Health. The scope of the research and preventive work conducted in the Department covers alcohol, drugs, tobacco and gambling issues. The two main tasks of the Department are (i) to research, produce and disseminate information on alcohol and drugs, substance use, addictions and their social and health-related effects and (ii) to develop prevention and good practices with a view to counteracting the onset and development of alcohol and drug problems and the damaging effects of smoking and other addictions. The number of staff hovers at approximately 60 people. The Department is organized into three units, one specialized in social sciences (the Alcohol and Drug Research Unit), another in laboratory analytics (the Alcohol and Drug Analytics Unit) and the third primarily in preventive work (the Addiction Prevention Unit). These units incorporate a rich variety and long traditions of both research and preventive work. The mixture of different disciplines creates good opportunities for interdisciplinary research projects and collaboration within the Department. Also, the fact that in the same administrative context there are both researchers and people specialized in preventive work opens up interesting possibilities for combining efforts from these two branches. Nationally, the Department is a key player in all its fields of interest. It engages in a great deal of cooperation both nationally and internationally, and among its strengths are the high-quality, regularly collected long-term data sets.     

Video capsule endoscopy in celiac disease: current clinical practice

OBJECTIVE: A complete examination of the small intestine is possible by video capsule endoscopy (VCE). The aim of this study was to evaluate current indications for performing VCE in celiac disease. METHODS: In all 84 celiac disease patients on a gluten‐free diet who had undergone VCE were enrolled at five centers in Europe. The indications, findings and clinical impact of VCE were recorded by a structured questionnaire. VCE was also carried out in 34 consecutive patients with untreated celiac disease (controls) in another center. RESULTS: Out of the 84 patients, 34 had overt symptoms and small intestinal histology compatible with refractory celiac disease. VCE was normal in 9 patients, and 7 had only proximal and one distal atrophy, 14 had intestinal ulcer and 2 an intestinal stricture. VCE was used in the adjustment of immunosuppressive treatment in 9 patients. In the remaining 50 patients, a VCE was performed because of less severe symptoms, 31 of which had an earlier histological recovery. The VCE showed proximal small bowel atrophy in 21 and distal atrophy in 3 patients, and 3 ulcers were seen. In this group the patients received mainly advice with a view to achieving better dietary compliance. Of the 34 newly detected celiac patients, 4 were normal, 27 proximal and 3 had distal small intestinal atrophy in the VCE. CONCLUSIONS: VCE has a definite impact on the management of refractory sprue. In the remaining patients with established celiac disease, the procedure plays a more limited role.     

Effect of platelet-activating factor (PAF) receptor blockers on smooth muscle cell replication in vitro and allograft arteriosclerosis in vivo

Platelet-activating factor (PAF) stimulates smooth muscle cell (SMC) replication both in vivo and in vitro. In this study we have investigated whether PAF receptor-blocking molecules modulate SMC replication in vitro and the generation of allograft arteriosclerosis in vivo. SMC cultures were established from baby rat aorta media and fibroblast control cultures from the adventitia. Identification of the cultured cell types was determined both by immunohistochemistry and electron microscopy. Both cell types replicated in culture with 10% fetal calf serum (FCS). The addition of PAF-C₁₈ enhanced, and the addition of three PAF receptor inhibitors — WEB 2086, WEB 2170, and BN 50739-reduced, SMC replication and protein synthesis in a dose-dependent fashion in vitro until toxic concentrations were reached. The most potent of these drugs, WEB 2170, was then delivered at the rate of 12 mg/kg per day to recipients of rat aortic allografts. The responses were quantitated by autoradiography after short-term labeling of the recipients with tritium-labeled thymidine (³H-TdR) and by quantitative morphology. Administration of the PAF receptor blocker had no impact on the replication of the inflammatory cells in the allograft adventitia nor on the replication of SMCs in the media and intima. Administration of the PAF receptor blocker delayed the generation of allograft arteriosclerosis slightly, but not significantly. These results suggest that PAF is not an essential component in the inflammatory cascade leading to allograft arteriosclerosis.     

Comparison of nitric oxide donors in lowering intraocular pressure in rabbits: role of cyclic GMP.

L-arginine-nitric oxide (NO) pathway participates in the physiology and in many pathological processes in the eye, such as glaucoma. The aim of the present study was to compare the ocular hypotensive effect of different NO-donors, and to get more information on the role of cyclic guanosine 3',5'-monophosphate (cGMP) in this process. The test compounds were administered topically or intravitreally in the eye of a normotensive rabbit. Intraocular pressure (IOP) was measured with a pneumatonometer after topical anesthesia. The metabolites of NO (nitrite, nitrate, NOx) and cGMP were assayed from the aqueous humor and plasma. NO-synthase (NOS) protein expression was assayed in the ciliary body by Western blotting. The maximal lowering of IOP was achieved as follows: atriopeptin III (concentration 78 (microM, decrease in IOP 50%), atriopeptin II (84 (microM 37%). 8-Br-cGMP (90 mM, 37%), zaprinast + 8-Br-cGMP (1 mM + 90 mM, 34%), L-arginine (1 mM, 29%), SNP (40 mM, 28%), nitrosocaptopril (100 mM, 28%), S-nitrosothiol (SNOG) (10 mM, 27%), YC-1 (10 (microM, 25%), zaprinast + SNP (1 mM + 40 mM, 22%), spermine NONOate (100 mM, 20%) [corrected]. The decrease in IOP lasted for 2-5 hr, except with atriopeptin II and III, when IOP values were first normalized in 6 hr and 2 days, respectively. In conclusion, the results of the present study indicate that by increasing the activity of L-arginine/NO/cGMP-pathway it is possible to lower IOP in rabbits equally to the currently used antiglaucomatous drugs.     

Effects of RM-beta-CD on sublingual bioavailability of Delta9-tetrahydrocannabinol in rabbits.

The purpose of the present study was to develop novel cyclodextrin-containing sublingual formulations of cannabinoids. Complexation of model cannabinoids, Delta(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD), with randomly methylated beta-cyclodextrin (RM-beta-CD) and hydroxypropyl-beta-cyclodextrin (HP-beta-CD), were studied by the phase-solubility method. Due to better complexation efficiency, RM-beta-CD was selected for further studies. Solid THC/RM-beta-CD and CBD/RM-beta-CD complexes were prepared by freeze-drying. The dissolutions of both THC and CBD in the presence and absence of RM-beta-CD were determined. THC was selected for in vivo studies: the pharmacokinetics of THC after both sublingual and oral administrations of ethanolic THC and THC/RM-beta-CD complex solutions were studied in rabbits. The aqueous solubility of CBD and THC increased as a function of CD concentration, showing A(L)- and A(P)-type diagrams for HP-beta-CD and RM-beta-CD, respectively. Dissolution rates of THC/RM-beta-CD and CBD/RM-beta-CD complexes were significantly (p < 0.05) higher than those of plain THC and plain CBD, respectively. The absolute bioavailability (F) of THC decreased in the following order: sublingual THC/RM-beta-CD solution (F = 12.1+/-1.4%; mean+/-S.D.; n = 4) > oral THC/RM-beta-CD solution (F = 4.0+/-6.0%) > or = sublingual ethanolic THC solution (F = 3.8+/-2.8%) > oral ethanolic THC solution (F = 1.3+/-1.4%). These results demonstrate that RM-beta-CD increases both the aqueous solubility and dissolution rate of these cannabinoids, making the development of novel sublingual formulation possible. These results also suggest that the sublingual administration of a THC/RM-beta-CD complex substantially increases the bioavailability of THC in rabbits.     

Mivacurium When Precedent by Pancuronium Becomes a Long-acting Muscle Relaxant

Background: To ensure rapid recovery of neuromuscular block, it might be useful to administer a short-acting relaxant after a long-acting one. Therefore, the interaction between pancuronium and mivacurium was investigated when mivacurium was administered during the recovery from pancuronium block.

Methods: After written informed consent, 41 adult patients were studied during propofol/alfentanil/nitrous oxide/oxygen anesthesia. Neuromuscular function was monitored using an electromyographic (EMG) method. After a stable EMG calibration response, cumulative doses of pancuronium were given to establish a 95% neuromuscular block. In the control group, an ED95 dose of 100 micro gram/kg mivacurium was administered instead of pancuronium. When the EMG response after pancuronium or mivacurium had recovered to 25% of the baseline, a single randomized intravenous bolus dose of 10 or 70 micro gram/kg mivacurium was given. Thereafter, spontaneous recovery of the neuromuscular function was recorded.

Results: The time from pancuronium until T1 25% EMG recovery was 38 +/-12 min (mean+/-SD). The respective times after 10 or 70 micro gram/kg mivacurium were 28+/-8 and 54+/-7 min in the pancuronium group or 3+/-1 (n = 3) and 10+/-4 min in the mivacurium group (P = 0.0001). Times to 95% EMG recovery after 10 or 70 micro gram/kg mivacurium were 77+/-14 and 97+/-16 min in the pancuronium group and 11+/-3 and 20+/-7 min in the mivacurium group, respectively (P < 0.0001). Recovery indexes after 10 or 70 micro gram/kg mivacurium were 26+/-4 and 22+/- 6 min in the pancuronium group or 7+/-3 (n = 3) and 5+/- 2 min in the mivacurium group, respectively (P < 0.0001). Times from the administration of 10 or 70 micro gram/kg mivacurium until train-of-four ratio 0.7 were 94+/-16 and 111+/-14 min in the pancuronium group and 12+/-4 and 22+/-8 min in the mivacurium group, respectively (P < 0.0001).     

Testicular infarction following ethanol embolization of a renal neoplasm

A case of infarction of the left testis secondary to transcatheter embolization of a malignant left renal tumor with absolute ethanol is presented. The mechanism producing this complication was due to the anomalous nature of the left testicular artery, originating from the left renal artery distal to the site of the balloon occlusion catheter. The importance of this anomaly is discussed and the literature reviewed.