Sorption, Desorption and Exchange of Cesium on Glaciofluvial Deposits

Distribution ratios and isotherms for Sorption, desorption and isotope-exchange of cesium (labelled with Cs-137) were measured on grain size fractions (<2mm) of quatemary glaciofluvial deposits. Sediment materials from two locations within Switzerland and synthetic groundwaters of different compositions were used. The investigated concentration range for cesium was 10"" — 10"' M. Cesium introduced into the system with the solid phase may influence the measurements at the lowest concentrations. Depending on the experimental conditions, the distribution ratios vary between 3 and 30'000 ml/g. The isotherms are non-linear. Normalization of the cesium concentration in the solid with the cation-exchange capacity leads to nearly identical isotherms for all size fractions of the two geographic locations. Desorption and exchange are retarded at the higher cesium concentrations. This can be explained by structural changes in clay minerals which dominate the Sorption of cesium on this material. Variations in the composition of the groundwater influence the Sorption of cesium only sHghtly; potassium and hydrogen ions are the main competitors

Genetics-Based Population Pharmacokinetics and Pharmacodynamics of Risperidone in a Psychiatric Cohort.

BACKGROUND: High interindividual variability in plasma concentrations of risperidone and its active metabolite, 9-hydroxyrisperidone, may lead to suboptimal drug concentration. OBJECTIVE: Using a population pharmacokinetic approach, we aimed to characterize the genetic and non-genetic sources of variability affecting risperidone and 9-hydroxyrisperidone pharmacokinetics, and relate them to common side effects. METHODS: Overall, 150 psychiatric patients (178 observations) treated with risperidone were genotyped for common polymorphisms in NR1/2, POR, PPARα, ABCB1, CYP2D6 and CYP3A genes. Plasma risperidone and 9-hydroxyrisperidone were measured, and clinical data and common clinical chemistry parameters were collected. Drug and metabolite concentrations were analyzed using non-linear mixed effect modeling (NONMEM(®)). Correlations between trough concentrations of the active moiety (risperidone plus 9-hydroxyrisperidone) and common side effects were assessed using logistic regression and linear mixed modeling. RESULTS: The cytochrome P450 (CYP) 2D6 phenotype explained 52% of interindividual variability in risperidone pharmacokinetics. The area under the concentration-time curve (AUC) of the active moiety was found to be 28% higher in CYP2D6 poor metabolizers compared with intermediate, extensive and ultrarapid metabolizers. No other genetic markers were found to significantly affect risperidone concentrations. 9-hydroxyrisperidone elimination was decreased by 26% with doubling of age. A correlation between trough predicted concentration of the active moiety and neurologic symptoms was found (p = 0.03), suggesting that a concentration &gt;40 ng/mL should be targeted only in cases of insufficient, or absence of, response. CONCLUSIONS: Genetic polymorphisms of CYP2D6 play an important role in risperidone, 9-hydroxyrisperidone and active moiety plasma concentration variability, which were associated with common side effects. These results highlight the importance of a personalized dosage adjustment during risperidone treatment

Treatment effects of Ginkgo biloba extract EGb 761® on the spectrum of behavioral and psychological symptoms of dementia: meta-analysis of randomized controlled trials.

ABSTRACTBackground:In randomized controlled trials, Ginkgo biloba extract EGb 761® has been found to be effective in the treatment of behavioral and psychological symptoms of dementia (BPSD). To assess the effects of EGb 761® on specific BPSD, we analyzed data from all randomized, placebo-controlled, at least 20-week, trials of EGb 761® enrolling patients with dementia (probable Alzheimer's disease (AD), probable vascular dementia or probable AD with cerebrovascular disease) who had clinically significant BPSD (Neuropsychiatric Inventory (NPI) total score at least 6). Data were pooled and joint analyses of NPI single item composite and caregiver distress scores were performed by meta-analysis with a fixed effects model. Four trials involving 1628 patients (EGb 761®, 814; placebo, 814) were identified; treatment duration was 22 or 24 weeks; the daily dose of EGb 761® was 240 mg in all trials. Pooled analyses including data from the full analysis sets of all trials (EGb 761®, 796 patients; placebo, 802 patients) revealed significant superiority of EGb 761® over placebo in total scores and 10 single symptom scores. Regarding caregiver distress scores, EGb 761®-treated patients improved significantly more than those receiving placebo in all symptoms except delusions, hallucinations, and elation/euphoria. The benefit of EGb 761® mainly consists of improvement in symptoms present at baseline, but the incidence of some symptoms was also decreased. Twenty two- to twenty four-week treatment with Ginkgo biloba extract EGb 761® improved BPSD (except psychotic-like features) and caregiver distress caused by such symptoms

Brain Aging in the Oldest-Old

Nonagenarians and centenarians represent a quickly growing age group worldwide. In parallel, the prevalence of dementia increases substantially, but how to define dementia in this oldest-old age segment remains unclear. Although the idea that the risk of Alzheimer's disease (AD) decreases after age 90 has now been questioned, the oldest-old still represent a population relatively resistant to degenerative brain processes. Brain aging is characterised by the formation of neurofibrillary tangles (NFTs) and senile plaques (SPs) as well as neuronal and synaptic loss in both cognitively intact individuals and patients with AD. In nondemented cases NFTs are usually restricted to the hippocampal formation, whereas the progressive involvement of the association areas in the temporal neocortex parallels the development of overt clinical signs of dementia. In contrast, there is little correlation between the quantitative distribution of SP and AD severity. The pattern of lesion distribution and neuronal loss changes in extreme aging relative to the younger-old. In contrast to younger cases where dementia is mainly related to severe NFT formation within adjacent components of the medial and inferior aspects of the temporal cortex, oldest-old individuals display a preferential involvement of the anterior part of the CA1 field of the hippocampus whereas the inferior temporal and frontal association areas are relatively spared. This pattern suggests that both the extent of NFT development in the hippocampus as well as a displacement of subregional NFT distribution within the Cornu ammonis (CA) fields may be key determinants of dementia in the very old. Cortical association areas are relatively preserved. The progression of NFT formation across increasing cognitive impairment was significantly slower in nonagenarians and centenarians compared to younger cases in the CA1 field and entorhinal cortex. The total amount of amyloid and the neuronal loss in these regions were also significantly lower than those reported in younger AD cases. Overall, there is evidence that pathological substrates of cognitive deterioration in the oldest-old are different from those observed in the younger-old. Microvascular parameters such as mean capillary diameters may be key factors to consider for the prediction of cognitive decline in the oldest-old. Neuropathological particularities of the oldest-old may be related to “longevity-enabling” genes although little or nothing is known in this promising field of future research

Oxidation of iodide and iodine on birnessite (δ-MnO2) in the pH range 4-8

The oxidation of iodide by synthetic birnessite (δ-MnO2) was studied in perchlorate mediain the pH range 4-8. Iodine (I2) was detected as an oxidation product that was subsequently further oxidized to iodate (IO3). The third order rate constants, second order on iodide and first order on manganese oxide, determined by extraction of iodine in benzene decreased with increasing pH (6.3-7.5) from 1790 to 3.1 M2 s1. Both iodine and iodate were found to adsorb significantly on birnessite with an adsorption capacity of 12.7 mM/g for iodate at pH5.7. The rate of iodine oxidation by birnessite decreased with increasing ionic strength, which resulted in a lower rate of iodate formation. The production of iodine in iodide-containing waters in contact with manganese oxides may result in the formation of undesired iodinated organic compounds (taste and odor, toxicity) in natural and technical systems. The probability of the formation of such compounds is highest in the pH range 5-7.5. For pH 7.5, iodide is not oxidized to a significant extent

Life events, salivary cortisol, and cognitive performance in nondemented subjects: a population-based study.

Older people are particularly exposed to stressful events, known to activate the hypothalamus-pituitary-adrenal axis resulting in increased cortisol levels. High cortisol has been associated with deleterious effects on cognition. We hypothesized that stressful life events could increase cortisol secretion leading to cognitive impairment. A cross-sectional analysis was conducted using data from Colaus/PsyColaus, a longitudinal population-based study among Lausanne residents. Salivary cortisol samples were obtained from 796 nondemented subjects aged at least 65. A neuropsychological battery was used to assess cognitive performance and determine the Clinical Dementia Rating Sum of Boxes (CDRSOB). Lifetime life events and their subjective impact were assessed using a validated questionnaire. The total impact of life events was associated neither with cortisol area under the curve (AUC) nor with CDRSOB nor with any cognitive domain performance. The CDRSOB was associated with the cortisol AUC, controlling for age, sex, body mass index, education and depressive symptoms (p = 0.003; B = 0.686 [0.240; 1.333]; r = 0.114). This association between CDRSOB and the cortisol AUC remained significant after controlling for life events total impact (p = 0.040; B = 0.591 [0.027; 1.155]; r = 0.106). These findings do not support the hypothesis that stressful life events increase cortisol secretion leading to cognitive impairment. The association of higher cortisol levels with poorer cognition might be not a mere reflection of stressful events but rather explained by other factors, yet to be elucidated