The Neurosteroid Allopregnanolone Is Reduced in Prefrontal Cortex in Alzheimer’s Disease

BACKGROUND: Few data are currently available investigating neurosteroids (NS) in Alzheimer's disease (AD). The NS allopregnanolone may be decreased in serum and plasma in patients with AD, but it is unclear if allopregnanolone is also reduced in brain. Because a number of NS exhibit neuroprotective effects and impact cognitive performance in rodent models, these molecules may be relevant to the pathophysiology of neurodegenerative disorders. We therefore investigated prefrontal cortex (PFC) NS levels in AD. METHODS: Neurosteroid levels (allopregnanolone, pregnenolone, dehydroepiandrosterone [DHEA]) were determined in postmortem PFC in 14 male subjects with AD and 15 cognitively intact male control subjects by gas chromatography/mass spectrometry preceded by high-performance liquid chromatography purification. RESULTS: Subjects with AD exhibit significant reductions in allopregnanolone compared with cognitively intact control subjects (median levels = 2.50 ng/g vs. 5.59 ng/g, respectively; p = .02). Allopregnanolone levels are inversely correlated with neuropathological disease stage (Braak), r = -.49, p = .007. Median DHEA levels are elevated in subjects with AD (p = .01). CONCLUSIONS: Subjects with AD demonstrate significant reductions in PFC allopregnanolone levels, a finding that may be relevant to neuropathological disease stage severity. Neurosteroids may have utility as candidate biomarkers in AD.     

Optimizing the efficiency of high-field multivoxel spectroscopic imaging by multiplexing in space and time.

A new strategy to yield information from the maximum number of voxels, each at the optimum signal-to-noise ratio (SNR) per unit time, in MR spectroscopic imaging (MRSI) is introduced. In the past, maximum acquisition duty-cycle was obtained by multiplexing in time several single slices each repetition time (TR), while optimal SNR was achieved by encoding the entire volume of interest (VOI) each TR. We show that optimal SNR and acquisition efficiency can both be achieved simultaneously by multiplexing in space and time several slabs of several slices, each. Since coverage of common VOIs in 3D proton MRSI in the human brain typically requires eight or more slices, at 3 T or higher magnetic fields, two or more slabs can fit into the optimum TR (approximately 1.6 s). Since typically four or less slices would then fit into each slab, Hadamard encoding is favored in that direction for slice profile reasons. It is demonstrated that per fixed examination length, the new method gives, at 3 T, twice as many voxels, each of the same SNR and size, compared with current 3D chemical shift imaging techniques. It is shown that this gain will increase for more extensive spatial coverage or higher fields.     

Introducing dental students to clinical patient care: The complete denture prosthodontics transition clinic

Using complete denture treatment as an introduction to clinical patient care for dental students, the purposes of the Complete Denture Prosthodontics Transition Clinic at the University of Colorado School of Dentistry are to reduce the time lapse between the preclinical complete denture prosthodontics course and the first denture patient experience, and to encourage development of student self-confidence and skills. In the 2002 spring semester, faculty at the University of Colorado School of Dentistry initiated the Complete Denture Prosthodontics Transition Clinic for DS-II (second-year) dental students, as an introduction to clinical patient care. Each patient was assigned to a team of two dental students. Three Division of Prosthodontics faculty members staffed each clinic session, providing a student-to-faculty ratio of approximately 6.6:1 and a patient-to-faculty ratio of approximately 3.3:1. All DS-II students in the Class of 2004 delivered their first complete dentures no later than 8 months (average, 184 days) after the last day of the preclinical complete denture prosthodontics course. The time from the diagnostic appointment through the denture placement appointment averaged 39 days for patients treated in this program, compared with an average of 98 days or more for previous classes. The program was successful in achieving the goal of reducing the time lapse between the preclinical complete denture prosthodontics course and the first denture patient experience.     

Peri-sleep-onset cortisol levels in children and adolescents with affective disorders.

BACKGROUND: Changes in the hypothalamic-pituitary-adrenal (HPA) axis, as evidenced by patterns of cortisol secretion, have been of interest in understanding depression and anxiety disorders across the life span. Previous studies of pediatric depression have pointed to the period around sleep onset as a key time point for observing alterations in cortisol secretion associated with affective disorders. Evidence also indicates that pubertal development may influence the expression of HPA dysregulation. We hypothesized that adolescents with depression and youth with anxiety disorders exhibit elevated peri-sleep-onset cortisol. METHODS: Plasma cortisol was sampled every 20 min around sleep onset from children and adolescents with major depressive disorder (n = 116), anxiety disorders (n = 32), or no history of psychiatric disorder (control; n = 76). Sleep onset was determined by polysomnography. Classification of participants as children or adolescents was based on Tanner staging of pubertal maturation. RESULTS: Children with anxiety disorders had higher peri-sleep-onset cortisol than children with depression or control children. Adolescents with depression had marginally higher peri-sleep-onset cortisol than control adolescents and significantly higher peri-sleep-onset cortisol than children with depression. CONCLUSIONS: Depression and anxiety are associated with altered cortisol secretion around sleep onset, and these changes appear to be influenced by pubertal maturation.     

Platelet-rich fibrin (PRF): a second-generation platelet concentrate. Part I: technological concepts and evolution.

Platelet-rich fibrin (PRF) belongs to a new generation of platelet concentrates geared to simplified preparation without biochemical blood handling. In this initial article, we describe the conceptual and technical evolution from fibrin glues to platelet concentrates. This retrospective analysis is necessary for the understanding of fibrin technologies and the evaluation of the biochemical properties of 3 generations of surgical additives, respectively fibrin adhesives, concentrated platelet-rich plasma (cPRP) and PRF. Indeed, the 3-dimensional fibrin architecture is deeply dependent on artificial clinical polymerization processes, such as massive bovine thrombin addition. Currently, the slow polymerization during PRF preparation seems to generate a fibrin network very similar to the natural one. Such a network leads to a more efficient cell migration and proliferation and thus cicatrization.     

Etanercept decreases tumor necrosis factor-α activity in chronic wound fluid

High levels of tumor necrosis factor-alpha (TNF-alpha), a pro-inflammatory cytokine, are present in the wound fluid of chronic nonhealing wounds. This leads to increased inflammation, cytokine expression, and ultimately results in impaired wound healing and tissue destruction. Etanercept is a recombinant fusion protein that consists of the soluble TNF receptor (p75) linked to the Fc portion of human IgG1. It is an effective inhibitor of TNF-alpha and has been shown to provide rapid and sustained improvement in rheumatoid arthritis by acting as a soluble receptor binding TNF-alpha and preventing its proinflammatory activities. Therefore, the aim of this study was to determine whether Etanercept could inhibit TNF-alpha activity in chronic wound fluid. Wound fluid was collected from the venous leg ulcers of 16 different patients. The effect of Etanercept on TNF-alpha activity was evaluated using both a TNF-alpha bioassay and an enzyme-linked immunoassay. Etanercept was found to reduce the cytotoxic effect of chronic wound fluid on L929 fibroblasts by approximately 30% and neutralized TNF-alpha binding in the enzyme-linked immunoassay by up to 80%. Direct application of Etanercept to chronic wounds may therefore reduce the inflammatory activity of TNF-alpha, which could reduce the chronicity of venous leg ulcers and thus aid in the healing of these wounds.