Novel PET and Near Infrared Imaging Probes for the Specific Detection of Bacterial Infections Associated With Cardiac Devices.

OBJECTIVES: The aim of this study was to develop imaging agents to detect early stage infections in implantable cardiac devices. BACKGROUND: Bacteria ingest maltodextrins through the specific maltodextrin transporter. We developed probes conjugated with either a fluorescent dye (maltohexaose fluorescent dye probe [MDP]) or a F-18 (F18 fluoromaltohexaose) and determined their usefulness in a model of infections associated with implanted cardiac devices. METHODS: Stainless steel mock-ups of medical devices were implanted subcutaneously in rats. On post-operative day 4, animals were injected with either Staphylococcus aureus around the mock-ups to induce a relatively mild infection or oil of turpentine to induce noninfectious inflammation. Animals with a sterile implant were used as control subjects. On post-operative day 6, either the MDP or F18 fluoromaltohexaose was injected intravenously, and the animals were scanned with the appropriate imaging device. Additional positron emission tomography imaging studies were performed with F18-fluorodeoxyglucose as a comparison of the specificity of our probes (n = 5 to 9 per group). RESULTS: The accumulation of the MDP in the infected rats was significantly increased at 1 h after injection when compared with the control and noninfectious inflammation groups (intensity ratio 1.54 ± 0.07 vs. 1.26 ± 0.04 and 1.20 ± 0.05, respectively; p < 0.05) and persisted for more than 24 h. In positron emission tomography imaging, both F18 fluoromaltohexaose and F18 fluorodeoxyglucose significantly accumulated in the infected area 30 min after the injection (maximum standard uptake value ratio 4.43 ± 0.30 and 4.87 ± 0.28, respectively). In control rats, there was no accumulation of imaging probes near the device. In the noninfectious inflammation rats, no significant accumulation was observed with F18 fluoromaltohexaose, but F18 fluorodeoxyglucose accumulated in the mock-up area (maximum standard uptake value 2.53 ± 0.39 vs. 4.74 ± 0.46, respectively; p < 0.05). CONCLUSIONS: Our results indicate that maltohexaose-based imaging probes are potentially useful for the specific and sensitive diagnosis of infections associated with implantable cardiac devices.

Gender differences in acute coronary syndromes: focus on the women with ACS without an obstructing culprit lesion.

INTRODUCTION: The etiologies of acute coronary syndromes (ACS) in women expand beyond the traditional paradigm of obstructive epicardial atherosclerotic disease and plaque rupture. Fundamental differences in pathobiology and presentation can partially explain the gender disparity in ACS diagnosis and management, but there is also much we do not know about the spectrum of coronary artery disease in women. Areas covered: This review seeks to explain some key differences between men and women in terms of risk factors, pathophysiology, and clinical presentations, as well as identify areas where more data are needed, focusing on women presenting with ACS but without a culprit lesion to explain their presentation. Literature search was undertaken with PubMed and Google Scholar. Expert commentary: Women with acute coronary syndromes but without plaque rupture or obstructive epicardial atherosclerosis can be difficult to diagnose and manage. Improving care in this underdiagnosed and undertreated population will require early identification of at risk patients, development of better diagnostic strategies, and standardized implementation of guideline-based therapies.

Microvascular angina: an update on diagnosis and treatment.

Many patients with chest pain who are relieved to learn that they have no obstructive stenoses at diagnostic angiography are misclassified as having noncardiac chest pain. Only recently have we developed the conceptual framework and diagnostic tools to understand that ischemic heart disease is not exclusively caused by obstructive coronary artery disease, but often has its origin in the microcirculation. This article will focus on the diagnosis and treatment of microvascular angina as a cause of myocardial ischemia in patients with abnormal but 'normal appearing' coronary arteries.

Growth hormone-releasing peptide-2 suppresses vascular oxidative stress in ApoE-/- mice but does not reduce atherosclerosis.

GH-releasing peptide-2 (GHRP-2) is a synthetic peptide that increases circulating GH and IGF-I levels. It also binds to CD36, a scavenger receptor for oxidized low-density lipoprotein (OxLDL), and may prevent cellular uptake of this proatherogenic complex. To determine its potential antiatherogenic effects, GHRP-2 (20 microg twice daily) was administered sc to ApoE(-/-) mice for 12 wk. GHRP-2 increased circulating IGF-I 1.2- to 1.6-fold and decreased circulating interferon-gamma by 66%. Although GHRP-2 did not alter atherosclerotic plaque area, it decreased aortic production of superoxide as assessed by dihydroethidium staining. GHRP-2 decreased aortic gene expression of 12/15-lipoxygenase by 92% and reduced the aortic expression of interferon-gamma and macrophage migration inhibitory factor. In cultured aortic smooth muscle cells, GHRP-2 prevented the OxLDL-induced generation of peroxides, down-regulation of IGF-I receptor, and apoptosis. In macrophages, GHRP-2 reduced lipid accumulation with OxLDL exposure. In summary, GHRP-2 exerts antioxidant effects in vivo and in vitro but does not reduce plaque burden. The lack of an antiatherogenic effect may be due to GH-dependent effects in vivo, thereby blunting the effect of increased IGF-I.

Functional dissection of the baculovirus late expression factor-8 gene: sequence requirements for late gene promoter activation.

The late expression factor-8 gene (lef-8) of Autographa californica M nucleopolyhedrovirus encodes the largest subunit of the virally encoded DNA-directed RNA polymerase specific for the transcription of late and very late viral genes. The sequence of lef-8 predicts a C-terminal motif of 13 amino acids that is conserved in other polymerases. Detailed mutagenesis throughout lef-8 was performed, including this C-terminal motif, to define sequences required for late promoter activation. It was found that the conserved C-terminal motif was critical for late gene expression. In addition, regions throughout the entire lef-8-encoding sequence were important for optimal function, suggesting complex protein-protein and protein-DNA interrelationships in the late gene-specific viral transcriptosome.