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Background An inverse association between Parkinson disease (PD) and total vitamin D levels has been reported but it is unknown whether vitamin D from different sources, i.e. 25(OH)D2 (from diet and supplements) and 25(OH)D3 (mainly from sunlight exposure), all contribute to the association.

Objective The objective of the study was to characterize changes in the oral clearance (CL/F) of lamotrigine (LTG) over the course of pregnancy and the postpartum period through a model-based approach incorporating clinical characteristics that may influence CL/F, in support of developing clinical management guidelines. Methods Women receiving LTG therapy who were pregnant or planning pregnancy were enrolled. Maternal blood samples were collected at each visit. A pharmacokinetic analysis was performed using a population-based, nonlinear, mixed-effects model. Results A total of 600 LTG concentrations from 60 women (64 pregnancies) were included. The baseline LTG CL/F was 2.16 L/h with a between-subject variability of 40.6%. The influence of pregnancy on CL/F was described by gestational week. Two subpopulations of women emerged based on the rate of increase in LTG CL/F during pregnancy. The gestational age-associated increase in CL/F displayed a 10-fold higher rate in 77% of the women (0.118 L/h per week) compared to 23% (0.0115 L/h per week). The between-subject variability in these slopes was 43.0%. The increased CL/F at delivery declined to baseline values with a half-life of 0.55 weeks. Interpretation The majority of women had a substantial increase in CL/F from 2.16 to 6.88 L/h by the end of pregnancy, whereas 23% of women had a minimal increase. An increase in CL/F may correspond to decreases in LTG blood concentrations necessitating the need for more frequent dosage adjustments and closer monitoring in some pregnant women with epilepsy. Postpartum doses should be tapered to preconception dose ranges within 3 weeks of delivery.

Summary Objective Clinical and preclinical studies indicate that maternal stress during pregnancy may exert long-lasting adverse effects on offspring. This investigation sought to identify factors mediating the relationship between maternal and neonatal hypothalamic–pituitary–adrenal (HPA) axes in pregnant women with past or family psychiatric history. Patients Two hundred and five pairs of maternal and umbilical cord blood samples from a clinical population were collected at delivery. Measurements Maternal and neonatal HPA axis activity measures were plasma adrenocorticotrophic hormone (ACTH), total cortisol, free cortisol and cortisol-binding globulin concentrations. The effects of maternal race, age, body mass index, psychiatric diagnosis (DSM-IV), birth weight, delivery method and estimated gestational age (EGA) at delivery on both maternal and neonatal HPA axis measures were also examined. Incorporating these independent predictors as covariates where necessary, we evaluated whether neonatal HPA axis activity measures could be predicted by the same maternal measure using linear regression. Results Delivery method was associated with umbilical cord plasma ACTH and both total and free cord cortisol concentrations (T = 10·53–4·21; P

Objective: Basal levels of glucocorticoids, such as cortisol, are generally unaltered in bipolar disorder. However, neuroendocrine tests of glucocorticoid receptor (GR) function such as the dexamethasone suppression test (DST) are frequently abnormal. Neuropsychological impairment is well documented in healthy volunteers after administration of glucocorticoids and in patients with bipolar affective disorder. This suggests a potential link between neuropsychological and hypothalamic-pituitary-adrenal axis function. We examined the hypothesis that neuropsychological impairment in bipolar disorder is associated with abnormal GR function. Methods: Seventeen euthymic bipolar patients and 16 controls completed tests of verbal declarative and working memory (WM) tests and the DST. The correlation between neuroendocrine and neuropsychological function was examined. Results: Bipolar patients made significantly more errors of omission and commission on the WM paradigm and demonstrated impaired verbal recognition memory. Patients’ post-dexamethasone cortisol correlated with WM commission errors (rs = 0.64, p = 0.0006). No such relationship was evident in controls. Conclusion: Deficits in declarative memory and WM are evident in patients with bipolar disorder. The deficit in retrieval accuracy from WM appears to be correlated with abnormal GR function.

The objective biomization method developed by Prentice et al. (1996) for Europe was extended using modern pollen samples from Beringia and then applied to fossil pollen data to reconstruct palaeovegetation patterns at 6000 and 18,000 14C yr bp. The predicted modern distribution of tundra, taiga and cool conifer forests in Alaska and north-western Canada generally corresponds well to actual vegetation patterns, although sites in regions characterized today by a mosaic of forest and tundra vegetation tend to be preferentially assigned to tundra. Siberian larch forests are delimited less well, probably due to the extreme under-representation of Larix in pollen spectra. The biome distribution across Beringia at 6000 14C yr bp was broadly similar to today, with little change in the northern forest limit, except for a possible northward advance in the Mackenzie delta region. The western forest limit in Alaska was probably east of its modern position. At 18,000 14C yr bp the whole of Beringia was covered by tundra. However, the importance of the various plant functional types varied from site to site, supporting the idea that the vegetation cover was a mosaic of different tundra types.

Alpha- and beta-adrenergic blocking agents and imipramine inhibit the increased hyaluronate synthesis that may be induced in human synovial cultures by connective tissue activating peptide (CTAP). Considerations of drug concentration requirements, actions of analogues, and time studies all indicate that the adrenergic blockers do not act in this circumstance as conventional blockers of alpha or beta receptor sites. It is suggested that the membrane-stabilizing properties of these agents may be the important determinant for their limited "antiactivation" effect. Ethacrynic acid, a potent and more complete inhibitor of connective tissue activation, appears to act via a different mechanism.

Rheumatoid synovial cells grown in vitro demonstrated: a) increased rate of lactate formation, b) increased rate of glucose uptake, c) increased rate of hyaluronate synthesis, d) decreased sensitivity to exogenous activator and e) increased concentrations of an endogenous activator. Exogenous activator was shown to be capable of inducing cortisol unresponsiveness in relation to suppression of hyaluronate synthesis. Evidence that exogenous activator is not long retained by synovial cells suggests that elevated levels in rheumatoid cells are due to accentuated endogenous formation. Elevated activator peptide content of rheumatoid synovial cells provides an explanation for many of the differences between normal and rheumatoid synovial cells in vitro.