Multimodal Gamma Stimulation Improves Activity but not Memory in Aged Tgf344-AD Rats.

BACKGROUND: Multimodal sensory gamma stimulation is a treatment approach for Alzheimers disease that has been shown to improve pathology and memory in transgenic mouse models of Alzheimer's. Because rats are closer to humans in evolution, we tested the hypothesis that the transgenic rat line bearing human APP and PS1, line TgF344-AD, would be a good supplemental candidate to test the efficacy of this treatment. Current therapy approaches under investigation seek to utilize the immune response to minimize or degrade the accumulation of ß-amyloid plaque load in mouse models designed to overexpress Aß. However, many of these models lack some of the hallmarks of Alzheimer's disease, such as hyperphosphorylated tau and neuronal cell loss. The TgF344-AD transgenic rat model is a good candidate to bridge the gap between mouse models and clinical efficacy in humans. OBJECTIVE: The objective of this study was to use multimodal gamma stimulation at light and auditory modalities simultaneously to test whether this enhances memory performance as measured by the object location task and the spontaneous alternation task. METHODS: In our study, we designed and built a low-cost, easy-to-construct multimodal light and sound gamma stimulator. Our gamma stimulation device was built using an Arduino microcontroller, which drives lights and a speaker at the gamma frequency. We have included in this paper our device's parts, hardware design, and software architecture for easy reproducibility. We then performed an experiment to test the effect of multimodal gamma stimulation on the cognitive performance of fourteen-month-old TgF344-AD rats. Rats were randomly assigned to either an experimental group that received gamma stimulation or a control group that did not. Performance in a Novel Object Location (NOL) task and spontaneous alternation task was evaluated in both groups before and after the treatment. RESULTS: Multimodal gamma stimulation did not improve memory compared to unstimulated TgF344-AD rats. However, the gamma-stimulated rats did spend significantly more time exploring objects in the novel location task than the unstimulated rats. In the spontaneous alternation task, gamma-stimulated rats exhibited significantly greater exploratory activity than unstimulated controls. CONCLUSION: Multimodal gamma stimulation did not enhance memory performance in the object location task or the spontaneous alternation task. However, in both tasks, the treatment group had improved measures of exploratory activity relative to the untreated group. We conclude that several limitations could have contributed to this mixed effect, including aging complications, different animal models, or light cycle effects.

The prognostic value of B-type natriuretic peptide in patients with acute coronary syndromes.

BACKGROUND: Brain (B-type) natriuretic peptide is a neurohormone synthesized predominantly in ventricular myocardium. Although the circulating level of this neurohormone has been shown to provide independent prognostic information in patients with transmural myocardial infarction, few data are available for patients with acute coronary syndromes in the absence of ST-segment elevation. METHODS: We measured B-type natriuretic peptide in plasma specimens obtained a mean (+/-SD) of 40+/-20 hours after the onset of ischemic symptoms in 2525 patients from the Orbofiban in Patients with Unstable Coronary Syndromes-Thrombolysis in Myocardial Infarction 16 study. RESULTS: The base-line level of B-type natriuretic peptide was correlated with the risk of death, heart failure, and myocardial infarction at 30 days and 10 months. The unadjusted rate of death increased in a stepwise fashion among patients in increasing quartiles of base-line B-type natriuretic peptide levels (P< 0.001). This association remained significant in subgroups of patients who had myocardial infarction with ST-segment elevation (P=0.02), patients who had myocardial infarction without ST-segment elevation (P<0.001), and patients who had unstable angina (P<0.001). After adjustment for independent predictors of the long-term risk of death, the odds ratios for death at 10 months in the second, third, and fourth quartiles of B-type natriuretic peptide were 3.8 (95 percent confidence interval, 1.1 to 13.3), 4.0 (95 percent confidence interval, 1.2 to 13.7), and 5.8 (95 percent confidence interval, 1.7 to 19.7). The level of B-type natriuretic peptide was also associated with the risk of new or recurrent myocardial infarction (P=0.01) and new or worsening heart failure (P<0.001) at 10 months. CONCLUSIONS: A single measurement of B-type natriuretic peptide, obtained in the first few days after the onset of ischemic symptoms, provides powerful information for use in risk stratification across the spectrum of acute coronary syndromes. This finding suggests that cardiac neurohormonal activation may be a unifying feature among patients at high risk for death after acute coronary syndromes.

Association of white blood cell count with increased mortality in acute myocardial infarction and unstable angina pectoris. OPUS-TIMI 16 Investigators.

We observed in a study of 7,651 patients with acute coronary syndromes that a white blood cell (WBC) count of > 10,000 was associated with increased 30-day and 10-month mortality (6.2% vs 3.2% to 3.6% for WBC count < 10,000; p < 0.000). With its simplicity and widespread availability, WBC count could serve as a simple, inexpensive, new tool for risk stratification in acute coronary syndromes.