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Histamine H3 receptor ligands have been proposed to be of potential therapeutic interest for the treatment of different central nervous system disorders; however, the psychopharmacological properties of these drugs have not been studied extensively. In this work, we investigated the possible involvement of histamine H3 receptor function in experimental models of anxiety (elevated plus-maze) and depression (forced swimming test). Male Sprague-Dawley rats were treated i.p. with the histamine H3 receptor agonist R-alpha-methylhistamine (10 mg/kg) or the histamine H3 receptor antagonist thioperamide (0.2, 2 and 10 mg/kg) and 30 min afterwards the time spent in the open arms of an elevated plus-maze was registered for 5 min. The immobility time of male OF1 mice in the forced swimming test was recorded for 6 min, 1 h after the i.p. administration of R-alpha-methylhistamine (10 and 20 mg/kg), thioperamide (0.2, 2, 10 and 20 mg/kg) or another histamine H3 receptor antagonist, clobenpropit (5 mg/kg). The locomotor activity of mice was checked in parallel by means of an activity meter. Both saline controls and active drug controls were used in all the paradigms. Neither thioperamide nor R-alpha-methylhistamine significantly changed animal behaviour in the elevated plus-maze. R-alpha-methylhistamine and the higher dose of thioperamide assayed (20 mg/kg) were also inactive in the forced swimming test. By contrast, thioperamide (0.2-10 mg/kg) dose-dependently decreased immobility, the effect being significant at 10 mg/kg (33% reduction of immobility); clobenpropit produced an effect qualitatively similar (24% reduction of immobility). None of these histamine H3 receptor antagonists affected locomotor activity. These preliminary results suggest that the histamine H3 receptor blockade could be devoid of anxiolytic potential but have antidepressant effects. Besides, the stimulation of these receptors does not seem to be followed by changes in the behavioural parameters studied.

BackgroundTo compare thermoplastic masks (TMP) and vacuum cushion system (VCS) to assess differences in interfraction set up accuracy in patients treated with stereotactic radiotherapy (SBRT) for oligometastatic lung cancer. Secondarily, to survey radiotherapy technologists to assess their satisfaction with the two systems.MethodsRetrospective study of patients treated with lung SBRT between 2008 to 2012 at our institution. Immobilization was performed for 73 treatment sessions (VCS = 40; TMP = 33). A total of 246 cone-beams were analysed. Patients considered ineligible for surgery with a life expectancy ≥6 months and performance status > 1 were included. Target lesion location was verified by cone beam computed tomography (CBCT) prior to each session, with displacements assessed by CBCT simulation prior to each treatment session. Couch shifts were registered prospectively in vertical, longitudinal, and latero-lateral directions to obtain Kernel coordinates (3D representation). Technologists were surveyed to assess their satisfaction with indexing, positioning, and learning curve of the two systems. Setup displacements were obtained in all patients for each treatment plan and for each session. To assess differences between the immobilization systems, a t-test (Welch) was performed.ResultsMean displacements for the TMP and VC systems, respectively, were as follows: session one, 0.64 cm vs 1.05 cm (p = 0.0002); session two, 0.49 cm vs 1.02 cm (p < 0.0001), and session three, 0.56 vs 0.97 cm (p = 0.0011). TMP resulted in significantly smaller shifts vs. VCS in all three treatment sessions. Technologists rated the learning curve, set up, and positioning more highly for TMP versus VCS.ConclusionsDue to the high doses and steep gradients in lung SBRT, accurate and reproducible inter-fraction set up is essential. We found that thermoplastic masks offers better reproducibility with significantly less interfractional set up displacement than vacuum cushions. Moreover, radiotherapy technologists rated the TMP system higher. Taken together, these two findings suggest that TMP may be preferable to VCS. However, more research is needed to determine both inter- and intrafraction error to identify the optimal immobilisation system for use in lung SBRT.

Dynalog analysis provides a feasible method for investigating the optimal tolerance for MLC positioning in dynamic fields. In sliding window treatments, the tolerance of 2 mm was found to be adequate, although it can be reduced to 1.5 mm. In VMAT treatments, the typically used 5 mm tolerance is excessively high. Instead, a tolerance of 2.5 mm is recommended.

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Imerslund‐Gräsbeck syndrome is an autosomal recessive disease reported only in certain pure‐breed dogs. An 18‐month‐old, male neutered beagle cross‐breed was presented for evaluation of severe lethargy, progressive weakness and anorexia. Main clinicopathological findings included low body condition score (2.5/9), severe muscle atrophy, several neurological abnormalities, mild normochromic, normocytic, non‐regenerative anaemia, severe hypocobalaminemia and mild proteinuria. Extensive diagnostic tests ruled out most of differential diagnoses for the aforementioned clinicopathological abnormalities and genetic evaluation showed that the dog was heterozygous for two previously described mutations affecting the CUBN gene, the beagle and the border collie variants. The dog showed an excellent clinical response to oral cobalamin supplementation with no relapse after 4 months. In conclusion, this case creates awareness that Imerslund‐Gräsbeck syndrome should be considered even in mixed‐breed dogs with compatible clinical signs and that two different pathogenic CUBN mutations in compound heterozygosity can lead to a typical Imerslund‐Gräsbeck syndrome phenotype.

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