Size distribution of total and water-soluble fractions of particle-bound elements-assessment of possible risks via inhalation.

The size distribution of total and water-soluble elemental concentrations in six particle sizes <0.49, 0.49-0.97, 0.97-1.5, 1.5-3.0, 3.0-7.2, and 7.2-30 µm was investigated in Thessaloniki area, N. Greece, at two sites representing urban-traffic and urban-background character during the cold and warm period. The elements As, Cd, Cr, Cu, Pb, Ni, Zn, Ru, and Ir exhibited their highest mass portion in the fine particle mode (0.97-1.5 µm), whereas Al, Ba, Ca, Fe, and Mn occurred predominately in the coarse particle mode (3.0-7.2 µm). The water-soluble elemental fractions exhibited significant spatiotemporal variations and particle size dependence. Possible non-carcinogenic and carcinogenic risks associated with inhalation of particle-bound elements based on total and water-soluble concentrations were in acceptable levels. However, the cumulative risk for all potential particle-bound constituents has to be considered.

CSF soluble amyloid precursor proteins in the diagnosis of incipient Alzheimer disease.

OBJECTIVE: To explore if soluble amyloid precursor proteins (sAPP) in CSF improve the identification of patients with incipient Alzheimer disease (AD) in a group of patients with mild cognitive impairment (MCI). METHODS: A cohort study with follow-up assessments of 58 patients with MCI with baseline CSF sampling was conducted: 21 patients had progressed to probable AD (MCI-AD), 27 still had MCI, 8 had reverted to normal (MCI-NAD), and 2 patients with frontotemporal dementia (FTD) were excluded. Sixteen additional patients with FTD were included to explore the specificity of the CSF markers. CSF concentrations of sAPPα, sAPPß, tau, and Aß(1-42) were measured with sensitive and specific ELISAs. Associations between diagnostic status, CSF protein concentrations, and other patient characteristics were explored using multiple logistic regression analyses with stepwise variable selection. The optimal sensitivity and specificity of the best models were derived from receiver operating characteristic curves. RESULTS: The MCI-AD group had significantly higher sAPPß concentrations than the MCI-NAD and the FTD groups. A combination of sAPPß, tau, and age differentiated the MCI-AD and the MCI-NAD groups with a sensitivity of 80.00% and a specificity of 81.00%. The best model for the differentiation of the MCI-AD and the FTD groups included sAPPß and tau, and showed a sensitivity of 95.20% and a specificity of 81.20%. Aß(1-42) and sAPPα did not significantly contribute to the models. CONCLUSION: These findings suggest that sAPPß may be clinically useful, and superior to Aß(1-42), in the early and differential diagnosis of incipient AD.

Acute stress regulation of neuroplasticity genes in mouse hippocampus CA3 area--possible novel signalling pathways.

Stress exposure can lead to the precipitation of psychiatric disorders in susceptible individuals, but the molecular underpinnings are incompletely understood. We used forced swimming in mice to reveal stress-regulated genes in the CA3 area of the hippocampus. To determine changes in the transcriptional profile 4 h and 8 h after stress exposure microarrays were used in the two mouse strains C57BL/6J and DBA/2J, which are known for their differential stress response. We discovered a surprisingly distinct set of regulated genes for each strain and followed selected ones by in situ hybridisation. Our results support the concept of a phased transcriptional reaction to stress. Moreover, we suggest novel stress-elicited pathways, which comprise a number of genes involved in the regulation of neuronal plasticity. Furthermore, we focused in particular on dihydropyrimidinase like 2, to which we provide evidence for its regulation by NeuroD, an important factor for neuronal activity-dependent dendritic morphogenesis.

Mutation detection of the human glucocorticoid receptor alpha gene area coding for the hormone-binding domain by denaturing gradient gel electrophoresis.

Mutations in the hormone-binding domain of the human glucocorticoid receptor alpha (hGRalpha) gene have been detected in a variety of glucocorticoid resistance syndromes. Using the denaturing gradient gel electrophoresis technique, we developed a sensitive method for the detection of alterations in the gene area coding for the whole hormone-binding domain and part of the DNA-binding domain of the hGRalpha. This method can be applied for screening of glucocorticoid receptor gene alterations in glucocorticoid-dependent diseases.

Standardisation of elemental analytical techniques applied to provenance studies of archaeological ceramics: an inter laboratory calibration study.

Chemical analysis is a well-established procedure for the provenancing of archaeological ceramics. Various analytical techniques are routinely used and large amounts of data have been accumulated so far in data banks. However, in order to exchange results obtained by different laboratories, the respective analytical procedures need to be tested in terms of their inter-comparability. In this study, the schemes of analysis used in four laboratories that are involved in archaeological pottery studies on a routine basis were compared. The techniques investigated were neutron activation analysis (NAA), X-ray fluorescence analysis (XRF), inductively coupled plasma optical emission spectrometry (ICP-OES) and inductively coupled plasma mass spectrometry (ICP-MS). For this comparison series of measurements on different geological standard reference materials (SRM) were carried out and the results were statistically evaluated. An attempt was also made towards the establishment of calibration factors between pairs of analytical setups in order to smooth the systematic differences among the results.

Glucocorticoid receptor alpha and beta isoforms are not mutated in bipolar affective disorder.

The periodically hyperactive hypothalamic-pituitary-adrenal (HPA) axis in bipolar affective disorders, as well as the reported changes in the binding characteristics of the glucocorticoid receptor (GR), suggest the possible involvement of the GR in the aetiopathology of this disease. This was investigated by screening the coding sequences of both GR isoforms, GRalpha and GRbeta, for the presence of mutations. As a genetic predisposition has been implicated, we included in this study bipolar patients who were siblings. By RT-PCR of peripheral blood mononuclear cells from patients suffering from bipolar illness, using primers spanning the whole length of the GRalpha and GRbeta coding region and subsequent agarose gel electrophoresis, heteroduplex and sequence analyses, no GR mutations could be detected. Since glucocorticoid receptor activity can be modulated by agents other than the respective ligand (eg by growth factors, cytokines and stress signals), our results favor derangements in the modulation of GR activity by such agents and not in the primary structure of the receptor as aetiopathologic factors of bipolar disease.