An 40Ar/39Ar, Rb/Sr, and stable isotope study of micas in low-grade fold-and-thrust belt: An example from the Swiss Helvetic Alps

White micas in carbonate-rich tectonites and a few other rock types of large thrusts in the Swiss Helvetic fold-and-thrust belt have been analyzed by Ar-40/Ar-39 and Rb/Sr techniques to better constrain the timing of Alpine deformation for this region. Incremental Ar-40/Ar-39 heating experiments of 25 weakly metamorphosed (anchizone to low greenschist) samples yield plateau and staircase spectra. We interpret most of the staircase release spectra result from variable mixtures of syntectonic (neoformed) and detrital micas. The range in dates obtained within individual spectra depends primarily on the duration of mica nucleation and growth, and relative proportions of neoformed and detrital mica. Rb/Sr analyses of 12 samples yield dates of ca. 10-39 Ma (excluding one anomalously young sample). These dates are slightly younger than the Ar-40/Ar-39 total gas dates obtained for the same samples. The Rb/ Sr dates were calculated using initial Sr-87/Sr-86 ratios obtained from the carbonate-dominated host rocks, which are higher than normal Mesozoic carbonate values due to exchange with fluids of higher Sr-87/Sr-86 ratios (and lower O-18/O-16 ratios). Model dates calculated using Sr-87/Sr-86 values typical of Mesozoic marine carbonates more closely approximate the Ar-40/Ar-39 total gas dates for most of the samples. The similarities of Rb/Sr and Ar-40/Ar-39 total gas dates are consistent with limited amounts of detrital mica in the samples. The delta(18)O values range from 24-15%. (VSMOW) for 2-6 mum micas and 27-16parts per thousand for the carbonate host rocks. The carbonate values are significantly lower than their protolith values due to localized fluid-rock interaction and fluid flow along most thrust surfaces. Although most calcite-mica pairs are not in oxygen isotope equilibrium at temperatures of ca. 200-400 degreesC, their isotopic fractionations are indicative of either 1) partial exchange between the minerals and a common external fluid, or 2) growth or isotopic exchange of the mica with the carbonate after the carbonate had isotopically exchanged with an external fluid. The geological significance of these results is not easily or uniquely determined, and exemplifies the difficulties inherent in dating very fine-grained micas of highly deformed tectonites in low-grade metamorphic terranes. Two generalizations can be made regarding the dates obtained from the Helvetic thrusts: 1) samples from the two highest thrusts (Mt. Gond and Sublage) have all of their Ar-40/Ar-39 steps above 20 Ma, and 2) most samples from the deepest Helvetic thrusts have steps (often accounting for more than 80% of Ar-39 release) between 15 and 25 Ma. These dates are consistent with the order of thrusting in the foreland-imbricating system and increase proportions of neoformed to detrital mica in the more metamorphosed hinterland and deeply buried portions of the nappe pile. Individual thrusts accommodated the majority of their displacement during their initial incorporation into the foreland-imbricating system, and some thrusts remained active or were reactivated down to 15 Ma.

Long-term citalopram administration reduces responsiveness of HPA axis in patients with major depression: relationship with S-citalopram concentrations in plasma and cerebrospinal fluid (CSF) and clinical response.

RATIONALE: A dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is a well-documented neurobiological finding in major depression. Moreover, clinically effective therapy with antidepressant drugs may normalize the HPA axis activity. OBJECTIVE: The aim of this study was to test whether citalopram (R/S-CIT) affects the function of the HPA axis in patients with major depression (DSM IV). METHODS: Twenty depressed patients (11 women and 9 men) were challenged with a combined dexamethasone (DEX) suppression and corticotropin-releasing hormone (CRH) stimulation test (DEX/CRH test) following a placebo week and after 2, 4, and 16 weeks of 40 mg/day R/S-CIT treatment. RESULTS: The results show a time-dependent reduction of adrenocorticotrophic hormone (ACTH) and cortisol response during the DEX/CRH test both in treatment responders and nonresponders within 16 weeks. There was a significant relationship between post-DEX baseline cortisol levels (measured before administration of CRH) and severity of depression at pretreatment baseline. Multiple linear regression analyses were performed to identify the impact of psychopathology and hormonal stress responsiveness and R/S-CIT concentrations in plasma and cerebrospinal fluid (CSF). The magnitude of decrease in cortisol responsivity from pretreatment baseline to week 4 on drug [delta-area under the curve (AUC) cortisol] was a significant predictor (p<0.0001) of the degree of symptom improvement following 16 weeks on drug (i.e., decrease in HAM-D21 total score). The model demonstrated that the interaction of CSF S-CIT concentrations and clinical improvement was the most powerful predictor of AUC cortisol responsiveness. CONCLUSION: The present study shows that decreased AUC cortisol was highly associated with S-CIT concentrations in plasma and CSF. Therefore, our data suggest that the CSF or plasma S-CIT concentrations rather than the R/S-CIT dose should be considered as an indicator of the selective serotonergic reuptake inhibitors (SSRIs) effect on HPA axis responsiveness as measured by AUC cortisol response.

Association of N-acetylaspartate and cerebrospinal fluid Aβ42 in dementia.

The interplay of amyloid and mitochondrial function is considered crucial in the pathophysiology of Alzheimer's disease (AD). We tested the association of the putative marker of mitochondrial function N-acetylaspartate (NAA) as measured by proton magnetic resonance spectroscopy within the medial temporal lobe and cerebrospinal fluid amyoid-β42 (Aβ42), total Tau and pTau181. 109 patients were recruited in a multicenter study (40 mild AD patients, 14 non-AD dementia patients, 29 mild cognitive impairment (MCI) AD-type patients, 26 MCI of non-AD type patients). NAA correlated with Aβ42 within the AD group. Since the NAA concentration is coupled to neuronal mitochondrial function, the correlation between NAA and Aβ42 may reflect the interaction between disrupted mitochondrial pathways and amyloid production.