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Jane C.F. Chang Paul Ciaccio Patricia Schroeder Lindsay Wright Russell Westwood Anna-Lena Berg 《Journal of toxicologic pathology》2014,27(1):31-42
AZD3783, a cationic amphiphilic drug and a potent inhibitor of the 5-hydroxytryptamine
(5-HT1B) receptor, was explored as a potential treatment for depression. To
support clinical trials, repeat dose toxicity studies in rats and dogs were conducted.
Here we report toxicity findings in dogs after dosing from 1 to 3 months. In the 1-month
study, there were minimal neuronal vacuolation in the brain, a marked increase in liver
enzymes accompanied by hepatocellular degeneration/necrosis and phospholipidosis (PLD),
and PLD/cholecystitis in the gallbladder of animals dosed at 47 mg/kg/day. In the 3-month
study, neurotoxicity resulted in euthanasia of one animal dosed at 30 mg/kg/day after 86
days. Extensive pathologic changes were seen in all animals in retina epithelium
(inclusion bodies), brain (neuronal vacuolation, degeneration, or necrosis and nerve fiber
degeneration), spinal ganglia (vacuolation, degeneration, or necrosis), as well as sciatic
and optic nerves (degeneration). Pigment-laden macrophages were observed in the lung,
kidney, liver, gallbladder, bone marrow, gastrointestinal tract, and lymphoid tissues.
Also seen were vitrel and retinal hemorrhage in the eyes. A brain concentration and
pathology study showed that the concentration of AZD3783 in the brain was approximately 4
times higher than in the plasma after 4 weeks of dosing, however, they were similar in all
regions examined, and did not correlate with areas with pathologic findings. Our findings
with AZD3783 in dogs have not been reported previously with other CNS compounds that
effect through serotonergic pharmacology. 相似文献
2.
Karin Hultin Jäderlund DVM Kerstin Hansson DVM Anna-Lena Berg DVM pHd Anders Sjöström MD pHd Kristina Narfström DVM PHD 《Veterinary radiology & ultrasound》2003,44(5):581-588
To evaluate the age of fontanelle closure of normal kittens and the size of their lateral ventricles, 50 ultrasonographic examinations using the bregmatic fontanelle as an acoustic window were made. Seven kittens, laboratory animals, were included in the study. To verify the location of the lateral ventricle, two of the kittens were sacrificed as neonates. In one of them ink was injected prior to autopsy into one lateral ventricle under sonographic guidance. In a longitudinal study of five of the kittens, the skull depth and the depth of the central part of the lateral ventricle reproduced in a longitudinal view could be measured up to the age of about 5 months. During that period, the skull depth increased from a median value of 1.95 cm (1.92-1.98) in a seven-day-old cat to 2.58 cm (2.52-2.59) in a 154-day-old cat, while the afore-mentioned ventricle values increased from 0.3 mm to 1.1 mm. 相似文献
3.
Detailed spatial changes in foreststructure in a central Swedish landscape were examinedusing geographic information system techniques. First,the influence of grazing and burning on forest densityand structure in the 19th century landscape wereanalyzed. Then, the development of the landscapeduring the 20th century, together with the impactof modern forest management methods on foreststructure, were analyzed using historical sources. In1907, over 20% of the 2200 hectare study site wassparsely-wooded (12 m3 ha–1) with old trees.These areas have been reforested with single-storiedmiddle-aged and old pine stands (66 m3 ha–1in 1989) during the 20th century. Firesuppression and changes in land use from subsistence-to-industrialforestry, facilitated Norway spruceregeneration as undergrowth in open Scots pine standsafter logging. This natural regeneration has, to alarge extent, been cut down and replaced by pineafforestation. During the second half of the 20thcentury, the standing timber volume has steadilyincreased, while the mean age of the forest hasdecreased. Today's young dense forests will result inhigher timber values in the coming decades, but theforest has lost a range of ecological niches. 相似文献
4.
Wensman JJ Ilbäck C Hjertström E Blomström AL Gustavsson MH Jäderlund KH Ström-Holst B Belák S Berg AL Berg M 《Veterinary immunology and immunopathology》2011,141(1-2):162-167
Borna disease virus (BDV) is a neurotropic, negative-stranded RNA virus, which causes a non-suppurative meningoencephalomyelitis in a wide range of animals. In cats, BDV infection leads to staggering disease. In spite of a vigorous immune response the virus persists in the central nervous system (CNS) in both experimentally and naturally infected animals. Since the CNS is vulnerable to cytotoxic effects mediated via NK-cells and cytotoxic T-cells, other non-cytolytic mechanisms such as the interferon (IFN) system is favourable for viral clearance. In this study, IFN-γ expression in the brain of cats with clinical signs of staggering disease (N=12) was compared to the expression in cats with no signs of this disease (N=7) by quantitative RT-PCR. The IFN-γ expression was normalised against the expression of three reference genes (HPRT, RPS7, YWHAZ). Cats with staggering disease had significantly higher expression of IFN-γ compared to the control cats (p-value ≤ 0.001). There was no significant difference of the IFN-γ expression in BDV-positive (N=7) and -negative (N=5) cats having clinical signs of staggering disease. However, as BDV-RNA still could be detected, despite an intense IFN-γ expression, BDV needs to have mechanisms to evade this antiviral immune response of the host, to be able to persist. 相似文献
5.
Anna-Lena Berg Dolores Gavier-Widén Kristina Nilsson Frederik Widén Mikael Berg Sune Gregorius Erik Agren Maria Erlandsson Torsten M?rner 《Journal of veterinary diagnostic investigation》2007,19(1):113-117
A neurologic disease affected a colony of endangered Fennoscandian arctic foxes (Alopex lagopus) kept in captivity for breeding purposes. Several outbreaks of disease occurred between 1994 and 2004. The clinical signs included ataxia, indications of anosmia, blindness, and abnormal behavior. The disease was characterized by severe necrotizing encephalitis affecting mostly the cranial cerebrum, basal ganglia, and olfactory bulbs. Investigations to identify the etiology of the disease included testing for several infectious agents known to cause encephalitis in carnivores. Tests for Toxoplasma gondii, Encephalitozoon cuniculi, Neospora caninum, canine distemper virus, rabies, adenovirus type 1, Borna disease virus, and Listeria monocytogenes were negative. The colony was closed, and the cause of the disease remains undetermined. 相似文献
6.
Anna-Maria Rautio Torbjörn Josefsson Anna-Lena Axelsson Lars Östlund 《Landscape Ecology》2016,31(2):337-349
Context
Past human land use has received increasing attention as an important driver of ecosystem change also in seemingly natural landscapes. Quantification of historical land use is therefore critical for assessing the degree of human impact and requires integration of ecology, history and archaeology.Objective
This study aims to assess and compare levels of resource use by different actors during 355 years across a large landscape of northern Sweden.Method
Data on resource use derived from case studies were extrapolated using demographic data to estimate harvested resources at the landscape scale. Here, we examined the use of the key-specie Scots pine by native Sami peoples and farmers and through commercial logging, and reconstructed historical forest conditions in order to interpret harvest levels and sustainability.Results
We show that (1) the pre-industrial use of Scots pine resources in Pite Lappmark was sustainable from a landscape perspective, and (2) that the early commercial logging, in contrast, was not sustainable. Large and old Scots pine trees were logged at a very high rate, reaching up to 300 % of the annual ingrowth.Conclusion
We suggest that historical landscape studies should incorporate analysis at different spatial scales, as such an approach can mirror the overall use of resources. Only then can land use data be applied across larger spatial scales, function as reference values and be compared to those of other regions, time-periods and types of human impact.7.
Anna-Lena Ungell 《Fish physiology and biochemistry》1989,6(3):157-165
The time course of appearance of catecholamine metabolites was studied in the spleen of cod,Gadus morhua, during perfusion with radioactively labelled noradrenaline and adrenaline at 10°C. The tlag for appearance of the metabolites ranged between 1.78 and 6.76 min after onset of perfusion for both amines, indicating a rapid disposition of catecholamines. Perfusion with noradrenaline resulted in mainly MOPEG, VMA and DOMA formation, while perfusion with adrenaline additionally resulted in MN formation. There was still formation of deaminated metabolites after denervation, which indicates an additional non-neuronal site of deamination. It is concluded from the study that the fate of noradrenaline and adrenaline within the cod spleen depends on their affinities for the two uptake mechanisms and an extraneuronal site of deamination of great importance cannot be excluded. 相似文献
8.
Matts Lindbladh Anna-Lena Axelsson Tove Hultberg Jörg Brunet Adam Felton 《Scandinavian Journal of Forest Research》2014,29(7):686-696
Mixed or broadleaf forests were once common in many regions of Northern Europe, whereas today conifers often dominate. The aim of the study was to investigate the spatial and temporal patterns and processes which underlie this transition to Picea abies dominance in southern Sweden. We use recently developed paleoecological methods to determine long-term changes in the relative abundance of tree species, and digitalized National Forest Inventory (NFI) databases to assess more recent changes in the spatial coverage of Picea throughout the region. The novel combination of the two databases reveals that Picea became a widespread and abundant species in many parts of southern Sweden around 1000 years ago. After a brief decline in abundance starting around 500 years ago, NFI data indicate a rapid increase in the volume of Picea between 1920 and 1950, prior to the large-scale introduction of Picea-dominated plantation forests. The available evidence suggests that abandonment of forest grazing and slash-and-burn cultivation, as well as selection cutting benefited the natural establishment and growth of Picea during the first half of the twentieth century. Hence, prior to the impacts of industrialized forestry that began in the 1950s, other processes were already favouring increased Picea abundance. 相似文献
9.
The aim of this study was to use finite element modeling (FEM) as a tool to analyze microwave scattering in wood and to verify
the model by measurements with a microwave scanner. A medical computed tomography scanner was used to measure distribution
of density and moisture content in a piece of Scots pine (Pinus sylvestris). Dielectric properties were calculated from measured values for cross sections from the piece and used in the model. Images
describing the distribution of the electric field and phase shift were obtained from the FEM simulation. The model was verified
by measurements with a scanner based on a microwave sensor. The results show that simulated values correspond well to measured
values. Furthermore, discontinuities in the material caused scattering in both the measured and the simulated values. The
greater the discontinuity in the material, the greater was the need for computational power in the simulation. 相似文献
10.
Current knowledge of patterns and abundance of deciduous trees in thepre-industrial landscape of boreal Sweden is limited. This is due to a dramatictransformation of the forest landscape during the last 100 years and the lackofrepresentative forest reserves. We used historical records to study change infive mixed deciduous forests between 1866 and 1999. The results show that largechanges occurred due to complex interactions between fire disturbance, firesuppression, logging and silviculture. Before fire suppression, the presence ofdeciduous trees was mainly determined by earlier fire influence. Laterselectivelogging disturbed natural succession and favoured regeneration of deciduoustrees. During the 20th century deciduous trees were removed bygirdling, thinning and herbicide spraying. Much of the mixed deciduous standschanged to coniferous stands between 1906–15 and 1969–70, and thendeciduous trees were totally removed from these stands between late 1960s and1999. Today mixed deciduous forest occurs mainly in young stands and on othersites than previously. Our results also show that large coniferous trees andmulti-aged forest occurred in all sites in the early 1900s. Most sites weredominated by coniferous species and forest dominated by deciduous treesoccurredonly in smaller areas. These results are not consistent with the current viewthat deciduous-dominated forest occupied substantial areas in boreal Swedenbefore fire suppression. Appropriate changes in forest management arediscussed,as is the value of historical data in interpreting changes in forestlandscapes.This revised version was published online in May 2005 with corrections to the Cover Date. 相似文献
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