Fluoxetine reverses the memory impairment and reduction in proliferation and survival of hippocampal cells caused by methotrexate chemotherapy

RATIONALE: Adjuvant cancer chemotherapy can cause long-lasting, cognitive deficits. It is postulated that these impairments are due to these drugs targeting neural precursors within the adult hippocampus, the loss of which has been associated with memory impairment. OBJECTIVES: The present study investigates the effects of the chemotherapy, methotrexate (MTX) on spatial working memory and the proliferation and survival of the neural precursors involved in hippocampal neurogenesis, and the possible neuroprotective properties of the antidepressant fluoxetine. METHODS: Male Lister hooded rats were administered MTX (75 mg/kg, two i.v. doses a week apart) followed by leucovorin rescue (i.p. 18 h after MTX at 6 mg/kg and at 26, 42 and 50 h at 3 mg/kg) and/or fluoxetine (10 mg/kg/day in drinking water for 40 days). Memory was tested using the novel location recognition (NLR) test. Using markers, cell proliferation (Ki67) and survival (bromodeoxyuridine/BrdU), in the dentate gyrus were quantified. RESULTS: MTX-treated rats showed a cognitive deficit in the NLR task compared with the vehicle and fluoxetine-treated groups. Cognitive ability was restored in the group receiving both MTX and fluoxetine. MTX reduced both the number of proliferating cells in the SGZ and their survival. This was prevented by the co-administration of fluoxetine, which alone increased cell numbers. CONCLUSIONS: These results demonstrate that MTX induces an impairment in spatial working memory and has a negative long-term effect on hippocampal neurogenesis, which is counteracted by the co-administration of fluoxetine. If translatable to patients, this finding has the potential to prevent the chemotherapy-induced cognitive deficits experienced by many cancer survivors

Effects of the fungicide metiram in outdoor freshwater microcosms: responses of invertebrates, primary producers and microbes

The ecological impact of the dithiocarbamate fungicide metiram was studied in outdoor freshwater microcosms, consisting of 14 enclosures placed in an experimental ditch. The microcosms were treated three times (interval 7 days) with the formulated product BAS 222 28F (Polyram®). Intended metiram concentrations in the overlying water were 0, 4, 12, 36, 108 and 324 μg a.i./L. Responses of zooplankton, macroinvertebrates, phytoplankton, macrophytes, microbes and community metabolism endpoints were investigated. Dissipation half-life (DT50) of metiram was approximately 1–6 h in the water column of the microcosm test system and the metabolites formed were not persistent. Multivariate analysis indicated treatment-related effects on the zooplankton (NOECcommunity = 36 μg a.i./L). Consistent treatment-related effects on the phytoplankton and macroinvertebrate communities and on the sediment microbial community could not be demonstrated or were minor. There was no evidence that metiram affected the biomass, abundance or functioning of aquatic hyphomycetes on decomposing alder leaves. The most sensitive populations in the microcosms comprised representatives of Rotifera with a NOEC of 12 μg a.i./L on isolated sampling days and a NOEC of 36 μg a.i./L on consecutive samplings. At the highest treatment-level populations of Copepoda (zooplankton) and the blue-green alga Anabaena (phytoplankton) also showed a short-term decline on consecutive sampling days (NOEC = 108 μg a.i./L). Indirect effects in the form of short-term increases in the abundance of a few macroinvertebrate and several phytoplankton taxa were also observed. The overall community and population level no-observed-effect concentration (NOECmicrocosm) was 12–36 μg a.i./L. At higher treatment levels, including the test systems that received the highest dose, ecological recovery of affected measurement endpoints was fast (effect period < 8 weeks)

Television and Dependency: A Case Study of Policy Making in Fiji and Papua New Guinea

Dependency theory continues to offer the development researcher attractive possibilities for heuristic claims about relationships of cultural or economic dependency between nations. However, as recent work on dependency theory-for example, by Larrain (1990) and Wallerstein (1990)-demonstrates, claims that dependency theory provides a valuable explanatory tool must take into account the specific social, cultural, and economic circumstances and idiosyncrasies of that country. That is, dependency theory must always be a possible conclusion, rather than a premise, of investigation. Dependency theory must be answerable, therefore, to empirical investigation. This paper details two empirical studies that furnish data for evaluating the validity of applying dependency theory to an understanding of the socioeconomic impact of televisual development in the Pacific. In the mid-1980s both Fiji and Papua New Guinea leaped enthusiastically into agreements with Australian media interests to introduce broadcast television into those countries. An examination of the policy formulation and decision-making processes of both Fijian and Papua New Guinean governments at the time shows that politicians in both Suva and Port Moresby did not cope well with the incompatible needs of profitoriented foreign media entrepreneurs and development-oriented national groups. This paper therefore focuses on the period of the early negotiations and dealmaking in the two countries, during the mid-1980s and on the social, political, and economic consequences of the resulting deals for both television institutions and their target audiences. It is argued that these consequences have been conducive to relations of cultural and economic dependency

Речевой конфликт как разновидность речевого взаимодействия

A computational molecular design strategy, complemented by UV/vis absorption and time-resolved electron paramagnetic resonance (EPR) spectra measurements, is employed to guide the search for active molecules for a room-temperature maser that can achieve continuous-wave operation. Focusing on linear polyacenes and diaza-substituted forms, our goal is to model how important maser properties are influenced by acene length and location of nitrogen substitution. We find that tetracene, its diaza-substituted forms (5,11-, 1,7-, and 2,8-diazatetracene), and anthracene possess singlet to triplet intersystem crossing rates highly favorable toward masing. The diaza-substituted forms of pentacene (6,13-, 5,12-, 1,8-, and 2,9-diazapentacene) also stand out as ideal candidates due to their similarity to the working pentacene prototype. A steady-state population analysis suggests the working conditions under which continuous-wave masing can be achieved for these molecules. Operational frequencies are estimated from calculated zero field splitting parameters