Implementation of improved postoperative care decreases the mortality rate of operated mice after an abundant 6-hydroxydopamine lesion of nigrostriatal dopaminergic neurons

A mouse model of Parkinson’s disease with an abundant lesion of nigrostriatal dopaminergic neurons can be achieved by stereotactic injection of 6-hydroxydopamine into the medial forebrain bundle. However, postoperative mortality can be excessively high without intensive postoperative care. Here, we show that improvements in stereotactic operations and postoperative care result in significant benefits for both animal well-being and research efficiency. Adopting a wide combination of mostly previously described improvements resulted in a decrease of postoperative mortality from 71% to 14% and an increase in successful abundant dopaminergic lesions from 46% to 81%. The techniques adopted are described in detail. In addition, we describe a simple protocol for gradual preoperative handling which can be utilized to decrease animal stress, aggressive and aversive behaviors, and to facilitate postoperative care and other subsequent handling. We propose that the implementation of these improvements greatly decreases the risk of animal suffering and that the improvements are worth adopting in any research group utilizing abundant 6-hydroxydopamine-induced dopaminergic lesions in mice. Suggestions for further improvement are also presented

Genetic lack of histamine upregulates dopamine neurotransmission and alters rotational behavior but not levodopa-induced dyskinesia in a mouse model of Parkinson’s disease

The brain histaminergic and dopaminergic systems closely interact, and some evidence also suggests significant involvement of histamine in Parkinson’s disease (PD), where dopaminergic neurons degenerate. To further investigate histamine-dopamine interactions, particularly in the context of PD, a genetic lack of histamine and a mouse model of PD and levodopa-induced dyskinesia were here combined. Dopaminergic lesions were induced in histidine decarboxylase knockout and wildtype mice by 6-hydroxydopamine injections into the medial forebrain bundle. Post-lesion motor dysfunction was studied by measuring drug-induced rotational behavior and dyskinesia. Striatal tissue from both lesioned and naïve animals was used to investigate dopaminergic, serotonergic and histaminergic biomarkers. Histamine deficiency increased amphetamine-induced rotation but did not affect levodopa-induced dyskinesia. qPCR measurements revealed increased striatal expression of D1 and D2 receptor, DARPP-32, and H3 receptor mRNA, and synaptosomal release experiments in naïve mice indicated increased dopamine release. A lack of histamine thus causes pre- and postsynaptic upregulation of striatal dopaminergic neurotransmission which may be reflected in post-lesion motor behavior. Disturbances or manipulations of the histaminergic system may thus have significant consequences for dopaminergic neurotransmission and motor behavior in both healthy and disease conditions. The findings also represent new evidence for the complex interplay between dopamine and histamine within the nigrostriatal pathway.Peer reviewe

Early phenology and growth trait variation in closely related European pine species

Closely related taxa occupying different environments are valuable systems for studying evolution. In this study, we examined differences in early phenology (bud set, bud burst) and early growth in a common garden trial of closely related pine species: Pinus sylvestris, P. mugo, and P. uncinata. Seeds for the trial were sourced from populations across the ranges of each species in Europe. Over first 4 years of development, clear differences were observed between species, while the most significant intraspecific differentiation was observed among plants from P. sylvestris populations from continental European locations. Trait differences within P. sylvestris were highly correlated with altitude and latitude of the site of origin. Meanwhile, P. mugo populations from the Carpathians had the earliest bud set and bud flush compared to other populations of the species. Overall, populations from the P. mugo complex from heterogeneous mountain environments and P. sylvestris from the Scottish Highlands showed the highest within-population variation for the focal traits. Although the three species have been shown to be genetically highly similar, this study reveals large differences in key adaptive traits both among and within species

Experimental and theoretical study of heterogeneous iron precipitation in silicon

Heterogeneous iron precipitation in silicon was studied experimentally by measuring the gettering efficiency of oxide precipitate density of 1×10exp10cm−3. The wafers were contaminated with varying iron concentrations, and the gettering efficiency was studied using isothermal annealing in the temperature range from 300 to 780°C. It was found that iron precipitation obeys the so called s-curve behavior: if iron precipitation occurs, nearly all iron is gettered. For example, after 30 min annealing at 700°C, the highest initial iron concentration of 8×10exp13cm−3 drops to 3×10exp12cm−3, where as two lower initial iron concentrations of 5×10exp12 and 2×10exp13cm−3 remain nearly constant. This means that the level of supersaturation plays a significant role in the final gettering efficiency, and a rather high level of supersaturation is required before iron precipitation occurs at all. In addition, a model is presented for the growth and dissolution of iron precipitates at oxygen-related defects in silicon during thermal processing. The heterogeneous nucleation of iron is taken into account by special growth and dissolution rates, which are inserted into the Fokker-Planck equation. Comparison of simulated results to experimental ones proves that this model can be used to estimate internal gettering efficiency of iron under a variety of processing conditions.Peer reviewe

The effect of sildenafil on pleural and peritoneal effusions after the TCPC operation

Background We evaluated whether the administration of sildenafil in children undergoing the TCPC operation shortened the interval from the operation to the removal of the pleural and peritoneal drains. Methods We retrospectively reviewed the data of 122 patients who had undergone the TCPC operation between 2004 and 2014. Patients were divided into two groups on the basis of their treatments. Sildenafil was orally administered pre-operatively in the morning of the procedure or within 24 hours after the TCPC operation to the sildenafil group (n = 48), which was compared to a control group (n = 60). Fourteen patients were excluded from the study. Results The primary outcome measure was the time from the operation to the removal of the drains. The study groups had similar demographics. The median [interquartile range] time for the removal of drains (sildenafil group 11 [8-19] vs control group 11 [7-16] d, P = .532) was comparable between the groups. The median [interquartile range] fluid balance on the first post-operative day was significantly higher (P = .001) in the sildenafil group compared with controls (47 [12-103] vs 7 [-6-67] mL kg(-1)). The first post-operative day fluid balance was a significant predictor for a prolonged need for drains in the multivariate analysis. Conclusions Sildenafil administration, pre-operatively or within 24 hours after the TCPC operation, did not reduce the required time for pleural and peritoneal drains but was associated with a significantly higher positive fluid balance.Peer reviewe