Differential effects of acute stress on spatial learning and memory in the open-field tower maze across the female estrous cycle.

The purpose of the present investigation was to test how acute stress and levels of circulating estrogens together influence acquisition and retention of spatial learning, as well as explorative behaviors in female rats. We used the hippocampus-dependent Open-field Tower Maze (OFTM) task to assess acquisition followed by a retention test (reacquisition) that was given 48 h later. Immediately prior to acquisition, experimental rats were exposed to an acute restraint stress and were trained under bright lights. Female rats' estrous cycles were tracked throughout training and testing. Exposure to stress did not affect learning when levels of estrogens were low (i.e., during estrus and metestrus). However, acute stress exposure significantly lowered spatial acquisition of the female rats in the phases with rising levels of estrogens (i.e., during diestrus and proestrus). Furthermore, this stress-induced diminishment during acquisition was evident at the beginning of the retention without any presentation of stress. The present findings provide insight about the interactive relationship between stress and sex hormones on cognitive functions.

Olfactory dysfunction in the 3xTg-AD model of Alzheimer's disease.

Alzheimer's disease (AD) is an incurable neurodegenerative disease in which the risk of development increases with age. People with AD are plagued with deficits in their cognition, memory, and basic social skills. Many of these deficits are believed to be caused by the formation of amyloid-ß plaques and neurofibrillary tangles in regions of the brain associated with memory, such as the hippocampus. However, one of the early, preclinical symptoms of AD is the loss of olfactory detection and discrimination. To determine if a mouse model of AD expresses the same olfactory dysfunction seen in human AD, 3xTg-AD mice were given a buried food test and, unlike previous studies, compared to their background and parental strains. Results showed that over 52 weeks, the 3xTg-AD mice took significantly longer to find the buried food than the control strains. The olfactory bulbs of the 3xTg-AD mice were removed, sliced, and stained using Congo red for histological analysis. Amyloid deposits were observed predominantly in the granule layer of the olfactory bulb beginning at 13 weeks of age in 3xTg-AD mice, but not in the control strains of mice. Further examination of the buried food test data revealed that 3xTg-AD females had a significantly longer latency to detect the buried food than males beginning at 26 weeks of age. Overall, this study provides further validation of the 3xTg-AD mouse model of AD and supports the idea that simple olfactory testing could be part of the diagnostic process for human AD.

Dupilumab, A Monoclonal Antibody for Atopic Dermatitis: A Review of Current Literature.

Atopic dermatitis results when aberrant barrier function and immune activation occur within the skin. Standard therapies for atopic dermatitis have fallen short, prompting efforts to discover novel therapeutics for this disease. Of these, dupilumab, a fully human monoclonal antibody that inhibits the actions of both IL-4 and IL-13, has shown the greatest promise. Clinical trials of systemic dupilumab in moderate-to-severe atopic dermatitis have demonstrated marked improvement in patient symptoms, including pruritus and clinically visible disease. Importantly, dupilumab treatment has been correlated with changes in the molecular signature of diseased skin, with reduction of both inflammatory and proliferative markers. Dupilumab recently received US FDA breakthrough therapy designation for atopic dermatitis, with ongoing trials in both adult and pediatric populations. Altogether, dupilumab has shed new light on the pathomechanisms driving atopic dermatitis and is making unprecedented advances towards highly effective control of this debilitating disease.

Treatment of early seropositive rheumatoid arthritis: a two-year, double-blind comparison of minocycline and hydroxychloroquine.

OBJECTIVE: To compare the efficacy of minocycline with that of a conventional disease-modifying antirheumatic drug (DMARD), hydroxychloroquine, in patients with early seropositive rheumatoid arthritis (RA). METHODS: Sixty patients with seropositive RA of <1 year's duration who had not been previously treated with DMARDs were randomized to receive minocycline, 100 mg twice per day, or hydroxychloroquine, 200 mg twice per day, in a 2-year, double-blind protocol. All patients also received low-dose prednisone. The primary end points of the study were 1) the percentage of patients with an American College of Rheumatology (ACR) 50% improvement (ACR50) response at 2 years, and 2) the dosage of prednisone at 2 years. RESULTS: Minocycline-treated patients were more likely to achieve an ACR50 response at 2 years compared with hydroxychloroquine-treated patients (60% compared with 33%, respectively; P = 0.04). Minocycline-treated patients were also receiving less prednisone at 2 years compared with the hydroxychloroquine group (mean 0.81 mg/day compared with 3.21 mg/day, respectively; P < 0.01). In addition, patients treated with minocycline were more likely to have been completely tapered off prednisone (P = 0.03). Trends favoring the minocycline treatment group were seen when outcomes were assessed according to components of the ACR core criteria set, with the differences reaching statistical significance for patient's global assessment of disease activity (P = 0.004). CONCLUSION: Minocycline is an effective DMARD in patients with early seropositive RA. Patients treated with minocycline were more likely to achieve an ACR50 response and did so while receiving less prednisone. In addition, minocycline-treated patients were more likely to have discontinued treatment with prednisone at 2 years.

Treatment of early seropositive rheumatoid arthritis with minocycline: four-year followup of a double-blind, placebo-controlled trial.

OBJECTIVE: Rheumatoid arthritis (RA) causes substantial morbidity and mortality, and current treatments are suboptimal. Recent studies have demonstrated the short-term efficacy of minocycline in the treatment of patients with early RA. This study was undertaken to compare patients treated with conventional therapy in the early phase of their RA and those treated with minocycline, after 4 years of followup. METHODS: Forty-six patients with seropositive RA of <1 year's duration had been enrolled in a double-blind study of minocycline (100 mg twice daily) versus placebo. After the blinded portion of the study (3-6 months, depending upon response), all patients were treated with conventional therapy. This report compares those patients randomized to receive placebo for 3 months and then conventional therapy for the duration of 4 years versus those originally randomized to receive minocycline. RESULTS: Twenty of the 23 original minocycline-treated patients and 18 of the 23 original placebo-treated patients were available for followup (mean 4 years). At followup, RA was in remission (American College of Rheumatology criteria) without disease-modifying antirheumatic drug (DMARD) or steroid therapy in 8 of the patients originally treated with minocycline compared with 1 patient in the placebo group (P = 0.02). Ten patients in the minocycline group versus 16 in the original placebo group currently require DMARD therapy (P = 0.02). CONCLUSION: Among patients with seropositive RA, remissions are more frequent and the need for DMARD therapy is less in those treated early in the disease course with minocycline compared with those treated with conventional therapy delayed by an average of only 3 months. Minocycline appears to be an effective therapy for early RA; further investigation into its mechanism of action is needed.

Treatment of early rheumatoid arthritis with minocycline or placebo: results of a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To determine if minocycline is an effective therapy for seropositive rheumatoid arthritis (RA) when used within the first year of disease. METHODS: The Rheumatoid Arthritis Investigational Network enrolled 46 patients with RA of <1 year duration into a 6-month study of minocycline (100 mg twice daily) versus placebo. All patients were rheumatoid factor positive. The primary end point of the study was successful completion of 6 months of treatment with no drug toxicity while maintaining 50% improvement in composite symptoms of arthritis. RESULTS: Eighteen of the 46 patients who were enrolled met 50% improvement criteria at 3 months, and maintained at least a 50% improvement for 6 months with no significant drug toxicity. Among them were 15 of the 23 patients (65%) treated with minocycline and 3 of 23 patients (13%) treated with placebo (P < 0.001). CONCLUSION: In patients with early seropositive RA, therapy with minocycline is superior to placebo.