Platelet Glutamate and Aspartate Uptake in Huntington's Disease

Abstract A possible involvement of amino acid uptake mechanisms in the etiology of the human neurodegenerative disease, Huntington's disease (HD), was investigated. Measurement of glutamate (Glu) and aspartate (Asp) uptake was performed in blood platelets, which have previously been shown to constitute a peripheral model system for central amino acid uptake processes. Analyses of Glu and Asp accumulation at 10⁻⁷ M and kinetic examination of the high affinity site for Glu indicate no significant differences between control and HD platelets. A genetically determined defect in amino acid uptake therefore does not seem to underlie the nerve cell loss observed in HD patients.     

Multidisciplinary approach to diagnosis and management of osteosarcoma – a review of the St Vincent's Hospital experience

Background

Osteosarcoma is the most common primary malignant bone tumour in children and young adults. Despite advances in the diagnosis and management of osteosarcoma, there have been few recent studies describing the experiences of tertiary referral centres. This paper aims to describe and discuss the clinical features, pre-operative work-up, management and outcomes of these patients at St Vincent's Hospital (Melbourne, Australia).

Methods

Retrospective study of fifty-nine consecutive patients managed for osteosarcoma at St Vincent's Hospital between 1995 and 2005.

Results

Median age at diagnosis was 21 (range, 11–84) years. Gender distribution was similar, with thirty-one male and twenty-eight female patients.Twenty-five patients had osteosarcoma in the femur, eleven each were located in the humerus and tibia, six were identified in the pelvis, and one each in the clavicle, maxilla, fibula, sacrum, ulna and radius.Pre-operative tissue diagnosis of osteosarcoma was obtained through computed tomography-guided percutaneous biopsy in over ninety percent of patients.Following initial therapy, over fifty percent of patients remained relapse-free during the follow-up period, with twelve percent and twenty-seven percent of patients documented as having local and distant disease recurrence, respectively. Of patients with recurrent disease, sixty-two percent remained disease-free following subsequent surgical intervention (most commonly, pulmonary metastatectomy).

Conclusion

Patient outcomes can be optimised through a multidisciplinary approach in a tertiary referral centre. At St Vincent's Hospital, survival and relapse rates of patients managed for osteosarcoma compare favourably with the published literature.

     

CHF5074 restores visual memory ability and pre‐synaptic cortical acetylcholine release in pre‐plaque Tg2576 mice

CHF5074, a new microglial modulator, attenuates memory deficit in Alzheimer's disease transgenic mice. In this study, the effect of an acute or subacute CHF5074 treatment on in vivo novel object recognition test and on [³H]Acetylcholine (ACh) and GABA release in pre‐plaque (7‐month‐old) Tg2576 mice have been compared with those induced by the γ‐secretase inhibitor LY450139 (semagacestat). Vehicle‐treated Tg2576 mice displayed an impairment of recognition memory compared with wild‐type animals. This impairment was recovered in transgenic animals acutely treated with CHF5074 (30 mg/kg), while LY450139 (1, 3, 10 mg/kg) was ineffective. In frontal cortex synaptosomes from vehicle‐treated Tg2576 mice, K⁺‐evoked [³H]ACh release was lower than that measured in wild‐type mice. This reduction was absent in transgenic animals subacutely treated with CHF5074 (30 mg/kg daily for 8 days), while it was slightly, not significantly, amplified by LY450139 (3 mg/kg daily for 8 days). There were no differences between the groups on spontaneous [³H]ACh release as well as spontaneous and K⁺‐evoked GABA release. These results suggest that CHF5074 has beneficial effects on visual memory and cortical cholinergic dysfunctions in pre‐plaque Tg2576 mice. Together with previous findings, these data suggest that CHF5074 could be a possible candidate for early Alzheimer's disease therapeutic regimens.     

Multiple stressors facilitate the spread of a non‐indigenous bivalve in the Mediterranean Sea

Aim

The introduction of non‐indigenous species (NIS) via man‐made corridors connecting previously disparate oceanic regions is increasing globally. However, the environmental and anthropogenic factors facilitating invasion dynamics and their interactions are still largely unknown. This study compiles and inputs available data for the NIS bivalve Brachidontes pharaonis across the invaded biogeographic range in the Mediterranean basin into a species distribution model to predict future spread under a range of marine scenarios.

Location

Mediterranean Sea.

Methods

A systematic review produced the largest presence database ever assembled to inform the selection of biological, chemical and physical factors linked to the spread of B. pharaonis through the Suez Canal. We carried out a sensitivity analysis to simulate current and future trophic and salinity scenarios. A species distribution model was run to determine key drivers of invasion, quantify interactive impacts arising from a range of trophic states, salinity conditions and climatic scenarios and forecast future trajectories for the spread of NIS into new regions under multiple‐parameter scenarios (based on the main factors identified from the systematic review).

Results

Impacts on invasion trajectory arising from climate change and interactions with increasing salinity from the new opening of the canal were the primary drivers of expansion across the basin, the effects of which were further enhanced by eutrophication. Predictions of the current distribution were most accurate when multiple stressors were used to drive the model. A habitat suitability index developed at a subcontinental scale from model outputs identified novel favourable conditions for future colonization at specific locations under 2030 and 2050 climatic scenarios.

Main conclusions

Future expansion of B. pharaonis will be enhanced by climate‐facilitated increased sea temperature, interacting with increasing pressures from salinity and eutrophication. The spatially explicit risk output maps of invasions represent a powerful visual product for use in communication of the spread of NIS and decision‐support tools for scientists and policymakers. The suggested approach, the observed distribution pattern and driving processes can be applied to other NIS species and regions by providing novel forecasts of species occurrences under future multiple stressor scenarios and the location of suitable recipient habitats with respect to anthropogenic and environmental parameters.     

Phylogenetic relationships of artiodactyls and cetaceans as deduced from the comparison of cytochrome b and 12S rRNA mitochondrial sequences

A data set of complete mitochondrial cytochrome b and 12S rDNA sequences is presented here for 17 representatives of Artiodactyla and Cetacea, together with potential outgroups (two Perissodactyla, two Carnivora, two Tethytheria, four Rodentia, and two Marsupialia). We include seven sequences not previously published from Hippopotamidae (Ancodonta) and Camelidae (Tylopoda), yielding a total of nearly 2.1 kb for both genes combined. Distance and parsimony analyses of each gene indicate that 11 clades are well supported, including the artiodactyl taxa Pecora, Ruminantia (with low 12S rRNA support), Tylopoda, Suina, and Ancodonta, as well as Cetacea, Perissodactyla, Carnivora, Tethytheria, Muridae, and Caviomorpha. Neither the cytochrome b nor the 12S rDNA genes resolve the relationships between these major clades. The combined analysis of the two genes suggests a monophyletic Cetacea +Artiodactyla clade (defined as "Cetartiodactyla"), whereas Perissodactyla, Carnivora, and Tethytheria fall outside this clade. Perissodactyla could represent the sister taxon of Cetartiodactyla, as deduced from resampling studies among outgroup lineages. Cetartiodactyla includes five major lineages: Ruminantia, Tylopoda, Suina, Ancodonta, and Cetacea, among which the phylogenetic relationships are not resolved. Thus, Suiformes do not appear to be monophyletic, justifying their split into the Suina and Ancodonta infraorders. An association between Cetacea and Hippopotamidae is supported by the cytochrome b gene but not by the 12S rRNA gene. Calculation of divergence dates suggests that the Cetartiodactyla could have diverged from other Ferungulata about 60 MYA.      

Antiinflammatory activity of adrenomedullin in the acetic acid peritonitis in rats

The antiinflammatory effect of ADM was studied in different models of inflammation and compared to the one of CGRP. Peptides were active against acetic acid-induced peritonitis in the rats. ADM and CGRP exerted the antiinflammatory effect at different doses, 400 and 20 ng/kg respectively, but with different efficacy (ADM >CGRP). This effect was blocked by pretreatment with CGRP (8-37) fragment or with L-NAME. No antiinflammatory activity was evidenced against serotonin- or carrageenin-induced rat paw edema. Our data suggest that ADM exerts antiinflammatory activity in the model characterized by a vascular component. This effect involves CGRP receptors and appears to be mediated by nitric oxide system.