The Effects of Dexamethasone on the Time to Pain Resolution in Dental Periapical Abscess.

BACKGROUND: Dental infections are frequently encountered in the emergency department (ED), with periapical abscesses being among the most painful. Traditional pain management strategies include local anesthetic injections, oral analgesics, and intravenous opioids. OBJECTIVES: We sought to identify an alternative pain management strategy with early use of dexamethasone as adjunct to conventional therapies for inflammation and pain at the site of infection. METHODS: We conducted a prospective, randomized, double-blind, placebo-controlled study comparing the analgesic effect of dexamethasone and placebo in ED patients with periapical abscess during a 2-year timeframe at two urban academic EDs. Adult patients presenting with physical examination findings consistent with a diagnosis of periapical abscess were randomized to receive oral dexamethasone or an identical placebo. Pain was assessed using the verbal numeric scale in person at discharge and via telephone at 12, 24, 48, and 72 h after discharge from the ED. RESULTS: Seventy-three patients were enrolled, with 37 receiving dexamethasone and 36 receiving placebo. Follow-up pain scores were obtained for 52 patients at 12, 24, 48, and 72 h. Ten patients from the dexamethasone group and 11 from placebo group were lost to follow-up. Patients who received dexamethasone reported a greater reduction in pain at 12 h compared with the placebo group (p = 0.029). Changes in pain scores from baseline and at 24, 48, and 72 h were not statistically significant. No adverse events were reported. CONCLUSIONS: Single-dose dexamethasone as adjunct to conventional medical management for pain caused by periapical abscess demonstrated a significant reduction in pain 12 h post treatment compared with placebo.

Mapping Depression in Schizophrenia: A Functional Magnetic Resonance Imaging Study.

Depressive symptoms are common in schizophrenia, often left untreated, and associated with a high relapse rate, suicidal ideation, increased mortality, reduced social adjustment and poor quality of life. The neural mechanisms underlying depression in psychosis are poorly understood. Given reports of altered brain response to negative facial affect in depressive disorders, we examined brain response to emotive facial expressions in relation to levels of depression in people with psychosis. Seventy outpatients (final N= 63) and 20 healthy participants underwent functional magnetic resonance imaging during an implicit affect processing task involving presentation of facial expressions of fear, anger, happiness as well as neutral expressions and a (no face) control condition. All patients completed Beck Depression Inventory (BDI-II) and had their symptoms assessed on the Positive and Negative Syndrome Scale (PANSS). In patients, depression (BDI-II) scores associated positively with activation of the left thalamus, extending to the putamen-globus pallidus, insula, inferior-middle frontal and para-post-pre-central gyri during fearful expressions. Furthermore, patients with moderate-to-severe depression had significantly higher activity in these brain regions during fearful expressions relative to patients with no, minimal, or mild depression and healthy participants. The study provides first evidence of enhanced brain response to fearful facial expressions, which signal an uncertain source of threat in the environment, in patients with psychosis and a high level of self-reported depression.

Design and synthesis of statine-based cell-permeable peptidomimetic inhibitors of human beta-secretase.

We describe the development of statine-based peptidomimetic inhibitors of human beta-secretase (BACE). The conversion of the peptide inhibitor 1 into cell-permeable peptidomimetic inhibitors of BACE was achieved through an iterative strategy of conceptually subdividing 1 into three regions: an N-terminal portion, a central statine-containing core, and a C-terminus. Replacement of the amino acid residues of 1 with moieties with less peptidic character was done with retention of BACE enzyme inhibitory activity. This approach led to the identification of the cell-permeable BACE inhibitor 38 that demonstrated BACE-mechanism-selective inhibition of Abeta secretion in human embryonic kidney cells.

A series of C-terminal amino alcohol dipeptide A beta inhibitors.

Potent, small molecule A beta inhibitors have been prepared that incorporate an alanine core bracketed by an N-terminal arylacetyl group and various C-terminal amino alcohols. The compounds exhibit stereospecific inhibition as demonstrated in an in vitro assay.