Madalina Macrea

Developing Biomarker Arrays Predicting Sleep and Circadian-Coupled Risks to Health

Janet M. Mullington, PhD1; Sabra M. Abbott, MD, PhD2; Judith E. Carroll, PhD3; Christopher J. Davis, MS, PhD4; Derk-Jan Dijk, PhD5; David F. Dinges, PhD6; Philip R. Gehrman, PhD7; Geoffrey S. Ginsburg, MD, PhD8; David Gozal, MD, MBA9; Monika Haack, PhD1; Diane C. Lim, MD10; Madalina Macrea, MD, MPH, PhD11,12; Allan I. Pack, MBChB, PhD, FRCP13; David T. Plante, MD14; Jennifer A. Teske, PhD15; Phyllis C. Zee, MD, PhD2

The neuroprotective effect of intranasally applied leptin against hypoxic neuronal injury

Hypoxia may result from hypoperfusion, as seen in the cardio-respiratory arrest. Subsequent to the acute neuronal damage, the delayed neuronal death ensues, and further neurons die within hours or days thereafter. An effective neuroprotective therapeutic agent should counteract one or, ideally, all well-established neuronal death pathways, i.e., excitotoxicity, oxidative stress and apoptosis. All these three mechanisms propagate through distinctive and mutual exclusive signal transduction pathway and contribute to the neuronal loss following the initial hypoxic-ischemic brain injury. Thus, the ideal therapeutic intervention against the hypoxic-ischemic neuronal injury should aim to prevent all three mechanisms of the neuronal death in a concerted effort. Recent studies demonstrated that intranasally administered leptin results in supra-physiological leptin levels at various regions of the brain (including hippocampus) within 30min of administration. We consider leptin to be an ideal neuroprotective agent, having targeted excitotoxicity (directly, by inhibiting AMDA and NMDA) oxidative stress (indirectly, by HIF1 mediation) and apoptosis (directly, by activating ERK 1/2 pathway) and hypothesize that intranasally administered leptin has neuroprotective effect against the neuronal hypoxic injury. If our hypothesis is confirmed, leptin administered before and/or soon after hypoxic injury, may be effective in minimizing the devastating sequelae of such event.

The peripheral neutrophils in subjects with COPD-OSA overlap syndromeand severe comorbidities: A feasible inflammatory biomarker?

BACKGROUND Overlap syndrome (OS) describes the association of obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) in a single individual. Subjects with OS have increased cardiovascular mortality which is presumed to be inflammation-mediated. As a clinical biomarker, an increased neutrophil count correlates with the severity of coronary artery stenosis. OBJECTIVES As little is known about the role of neutrophils in the underlying inflammatory mechanisms in OS, we aimed to assess the percentage of peripheral neutrophils (PPN) in OS vs in COPD alone. MATERIAL AND METHODS A cross-sectional study of patients with COPD and severe comorbidities, as defined by a Care Assessment Need score over 95, were seen in the Pulmonary Tele-Health Clinic at the Salem Veteran Affairs Medical Center, USA, over a 1-year period. Demographic and polysomnographic data, FEV1 and the Charlson Comorbidity Index (CCI) were extracted from the Electronic Medical Records. Obstructive sleep apnea was defined according to the American Academy of Sleep Medicine (AASM) guidelines. Serum inflammatory markers (PPN, CRP, fibrinogen and procalcitonin) were obtained after the Tele-Health appointment. RESULTS Out of the 38 subjects with COPD, 17 (44%) had OS. Compliance with continuous positive airway pressure therapy (CPAP) was excellent in 7 OS subjects (41%). There was a significant difference in the PPN of subjects with OS vs COPD alone, regardless of whether they were compliant (p = 0.03) with the CPAP therapy or not (p = 0.005). No differences in the severity of COPD, baseline comorbidity, smoking, or inflammatory markers were found between the OS and COPD-only subjects. Body mass index (BMI), COPD severity, smoking, and home oxygen therapy (HOT) use were not associated with PPN (p > 0.2). CONCLUSIONS Overlap syndrome subjects have higher PPN than those with COPD alone, regardless of their CPAP compliance. Our results could be used to motivate OS subjects to improve their lifestyles and to comply with drug therapies aimed at reducing cardiovascular disease (CVD).

Letter by Minciu Macrea et al Regarding Article, “Leptin Signaling in the Failing and Mechanically Unloaded Human Heart”

To the Editor: In their article “Leptin signaling in the failing and mechanically unloaded human heart,” McGaffin et al1 (November 2009 issue) indicate a cardioprotective role for leptin; based on the activation of signal transducer and activator of transcription-3 and AMP-activated kinase signaling, they suggest that the expression of leptin in …