| 1. |
- Bengtsson, Bengt-O
(författare)
-
On the hypersensitivity syndrome induced by the selective serotonin reuptake inhibiting antidepressant Zimeldine : A clinical and experimental study
- 1992
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Zimeldine, the first selective neuronal serotonin (5-H1) reuptake inhibitor to be registered as an antidepressant was withdrawn from common use due to an acute flu-like adverse syndrome comprising fever, myalgia and/or arthralgia and signs of disturbed liver function. A few of these patients also developed a peripheral neuropathy, in the most serious form a Guillain-Barré syndrome (GBS). The reaction was tentatively termed a hypersensitivity syndrome (HSS).Patients who had developed a HSS during zimeldine therapy (HSS-patients) were compared to control patients who tolerated the drug.No predictor to the HSS emerged concerning demographic data, psychiatric illness, previous medical history, medications with zimeldine or other drugs, other diseases, professional or nutritional circumstances. Nor was there any sign that HSS-patients who also developed neurological symptoms had a different profile of the HSS than other HSS-patients. Earlier zin1eldine treatment per se was not seen to predispose for development of a HSS or any other kind of adverse experience during subsequent therapy. The spectrum of adverse reactions was in agreement with those reported in previous studies and no new case of the GBS was revealed. The estimated frequency of HSS ranged from 0.63 to 3.4 % in spontaneous reports to the regnlatory authority and 1.4- 13% in a written inquiry. Among closely monitored inpatients 31 %developed a HSS. The mechanism for the HSS does not seem to be related primarily to the 5-HT reuptake inhibition as such. No HLA-associated disposition for the HSS was found. Nor was there any support for a HLA-associated disposition for depressive disorders. The pathogenetic mechanism for the HSS seems to involve an inlmunological response to antigens related to zimeldine.Zimeldine and its main primary metabolite norzimeldine both suppressed clinical signs of experimental allergic neuritis (EAN) in Lewis rats. Imrnunomodulatory effects in vitro of zimeldine, its metabolites norzimeldine and CPP 200 as well as of other monoamine reuptake inhibiting antidepressants were identified in the same EAN model.These observations call for further research on immunological mechanisms in the pathogenesis of mental disorders as well as on the potential role of drugs acting on the monoamine systems in the treatment of autoimmune diseases. The findings also justify a discussion on the application of immunological methods in the testing of new psychopharmacological drugs.Based on the presented results the tentatively used term for the adverse reactions to zimeldine, the hypersensitivity syndrome, seems justified.
|
|
| 2. |
- Stiernström, Sara, et al.
(författare)
-
Improved understanding of key elements governing the toxicity of energy ash eluates
- 2013
-
Ingår i: Waste Management. - : Elsevier BV. - 0956-053X .- 1879-2456. ; 33:4, s. 842-849
-
Tidskriftsartikel (refereegranskat)abstract
- Ash from incinerated waste consists mainly of a complex mixture of metals and other inorganic elements and should be classified based on its inherent hazardous effects according to EUs Waste Framework Directive. In a previous study, we classified eight eluates from ash materials from Swedish incineration plants, both chemically and ecotoxicologically (using bacteria, algae, crustacean and fish). Based on measured concentrations in the eluates together with literature acute toxicity data on the crustacean Nitocra spinipes we identified six elements (i.e. Zn, Cu, Pb, Al, K and Ca) potentially responsible for the observed ecotoxicity. However, comparing the used test methods with N. spinipes, the acute test was relatively insensitive to the eluates, whereas the (sub)chronic test (i.e. a partial life cycle test, investigating larval development ratio) was very sensitive. The overall aim of this follow-up study was to verify if the pinpointed elements could be responsible for the observed (sub)chronic toxicity of the eluates. Individual effect levels (i.e. NOEC values) for these six elements were therefore generated using the (sub)chronic test. Our results show that for six of the eight eluates, the observed ecotoxicity can be explained by individual elements not classified as ecotoxic (Al, K and Ca) according to chemical legislation. These elements will not be considered using summation models on elements classified as ecotoxic in solid material for the classification of H-14, but will have significant implications using ecotoxicological test methods for this purpose.
|
|
| 3. |
- Zhu, Junwei, et al.
(författare)
-
Genetic variation in the strongly canalized sex pheromone communication system of the European corn borer, Ostrinia nubilalis hubner (Lepidoptera; Pyralidae)
- 1996
-
Ingår i: Genetics. - 0016-6731. ; 144:2, s. 757-766
-
Tidskriftsartikel (refereegranskat)abstract
- The major difference in pheromone production between the so-called E and Z strains of the European corn borer Ostrinia nubilalis is controlled by two alleles at a single autosomal locus. E-strain females produce an (E)-11- tetradecenyl acetate pheromone with 1-3% of the Z isomer, whereas Z-strain females produce the opposite blend. In laboratory-reared insects we found that F1 females produced, on average, a 71:29 E/Z ratio, but the distribution was clearly bimodal. The variability in pheromone blend produced by heterozygous females could be explained by the existence of two different alleles in the Z strain which in combination with the E-strain allele for the major production locus cause the production of a component mixture either high or low in the E isomer. In addition, evidence was found for an independently inherited factor, existing in the E-strain, with a dominant effect on the amount of E isomer produced by females homozygous for Z- alleles at the major production locus. Thus, the low variability normally found in the pheromone mixture produced by O. nubilalis and other moth females may, by canalization, hide a considerable amount of underlying genetic variation.
|
|
