The contribution of neutrophils to bacteriophage clearance and pharmacokinetics in vivo.

With the increasing prevalence of antimicrobial-resistant bacterial infections, there is interest in using bacteriophages (phages) to treat such infections. However, the factors that govern bacteriophage pharmacokinetics in vivo remain poorly understood. Here, we have examined the contribution of neutrophils, the most abundant phagocytes in the body, to the pharmacokinetics of i.

The contribution of neutrophils to bacteriophage clearance and pharmacokinetics in vivo.

With the increasing prevalence of antimicrobial-resistant bacterial infections, there is great interest in using lytic bacteriophages (phages) to treat such infections. However, the factors that govern bacteriophage pharmacokinetics remain poorly understood. Here, we have examined the contribution of neutrophils, the most abundant phagocytes in the body, to the pharmacokinetics of intravenously administered bacteriophage in uninfected mice.

Rapid assessment of changes in phage bioactivity using dynamic light scattering.

Extensive efforts are underway to develop bacteriophages as therapies against antibiotic-resistant bacteria. However, these efforts are confounded by the instability of phage preparations and a lack of suitable tools to assess active phage concentrations over time. In this study, we use dynamic light scattering (DLS) to measure changes in phage physical state in response to environmental factors and time, finding that phages tend to decay and form aggregates and that the degree of aggregation can be used to predict phage bioactivity.

Gla-domain mediated targeting of externalized phosphatidylserine for intracellular delivery.

Phosphatidylserine (PS) is a negatively charged phospholipid normally localized to the inner leaflet of the plasma membrane of cells but is externalized onto the cell surface during apoptosis as well as in malignant and infected cells. Consequently, PS may comprise an important molecular target in diagnostics, imaging, and targeted delivery of therapeutic agents. While an array of PS-binding molecules exist, their utility has been limited by their inability to internalize diagnostic or therapeutic payloads.

Rapid assessment of changes in phage bioactivity using dynamic light scattering.

Extensive efforts are underway to develop bacteriophages as therapies against antibiotic-resistant bacteria. However, these efforts are confounded by the instability of phage preparations and a lack of suitable tools to assess active phage concentrations over time. Here, we use Dynamic Light Scattering (DLS) to measure changes in phage physical state in response to environmental factors and time, finding that phages tend to decay and form aggregates and that the degree of aggregation can be used to predict phage bioactivity.

Immunomodulation Therapy Using Tolerogenic Macrophages in a Rodent Model of Pulmonary Hypertension.

Inflammation plays a major role in the pathogenesis of pulmonary hypertension (PH). We sought to investigate the effects of a cell-based immunomodulation in a dysimmune model of PH. PH was induced in athymic nude rats using semaxinib (Su group,  = 6).

A novel roadmap connecting the H-MRS total choline resonance to all hallmarks of cancer following targeted therapy.

This review describes a cellular adaptive stress signalling roadmap connecting the H magnetic resonance spectroscopy (MRS) total choline peak at 3.2 ppm (tCho) to cancer response after targeted therapy (TT). Recent research on cell signalling, tCho metabolism, and TT of cancer has been retrospectively re-examined.

Molecular Imaging of Apoptosis in Atherosclerosis by Targeting Cell Membrane Phospholipid Asymmetry.

Background: Apoptosis in atherosclerotic lesions contributes to plaque vulnerability by lipid core enlargement and fibrous cap attenuation. Apoptosis is associated with exteriorization of phosphatidylserine (PS) and phosphatidylethanolamine (PE) on the cell membrane. Although PS-avid radiolabeled annexin-V has been employed for molecular imaging of high-risk plaques, PE-targeted imaging in atherosclerosis has not been studied.

Deep-learning-assisted diagnosis for knee magnetic resonance imaging: Development and retrospective validation of MRNet.

Background: Magnetic resonance imaging (MRI) of the knee is the preferred method for diagnosing knee injuries. However, interpretation of knee MRI is time-intensive and subject to diagnostic error and variability. An automated system for interpreting knee MRI could prioritize high-risk patients and assist clinicians in making diagnoses.

Deep learning for chest radiograph diagnosis: A retrospective comparison of the CheXNeXt algorithm to practicing radiologists.

Background: Chest radiograph interpretation is critical for the detection of thoracic diseases, including tuberculosis and lung cancer, which affect millions of people worldwide each year. This time-consuming task typically requires expert radiologists to read the images, leading to fatigue-based diagnostic error and lack of diagnostic expertise in areas of the world where radiologists are not available. Recently, deep learning approaches have been able to achieve expert-level performance in medical image interpretation tasks, powered by large network architectures and fueled by the emergence of large labeled datasets.

Molecular Imaging of Apoptosis in Ischemia Reperfusion Injury With Radiolabeled Duramycin Targeting Phosphatidylethanolamine: Effective Target Uptake and Reduced Nontarget Organ Radiation Burden.

Objectives: The purpose of this study was to evaluate the feasibility of imaging apoptosis in experimental ischemia-reperfusion model by technetium-99m (Tc)-labeled Duramycin, and compare it to an established tracer, Tc-labeled Annexin-V, which has a relative disadvantage of high radiation burden to nontarget organs.

Background: During apoptosis, the cell membrane phospholipids-phosphatidylserine (PS) and phosphatidylethanolamine (PE) are exposed and can be targeted by Annexin-V and Duramycin, respectively, for in vivo imaging. Identification of a reversible cell death process should permit therapeutic intervention to help reduce myocyte loss and left ventricle dysfunction.

Preparation of Tc99m-Labeled Pseudomonas Bacteriophage without Adversely Impacting Infectivity or Biodistribution.

Bacteriophages (phages) are ubiquitous viruses which have adapted to infect and replicate within target bacteria, their only known hosts, in a strain specific fashion with minimal cross infectivity. The recent steep rise in antibiotic resistance throughout the world has renewed interest in adapting phages for the imaging and treatment of bacterial infection in humans. In this article, we describe the current limitations surrounding the radiolabeling of phage for the imaging and treatment of bacterial infection and methods to overcome these difficulties.

Cardioprotective Effects of HSP72 Administration on Ischemia-Reperfusion Injury.

Background: Although early reperfusion is the most desirable intervention after ischemic myocardial insult, it may add to damage through oxidative stress.

Objectives: This study investigated the cardioprotective effects of a single intravenous dose of heat shock protein-72 (HSP72) coupled to a single-chain variable fragment (Fv) of monoclonal antibody 3E10 (3E10Fv) in a rabbit ischemia-reperfusion model. The Fv facilitates rapid transport of HSP72 into cells, even with intact membranes.

Targeted scVEGF/(177)Lu radiopharmaceutical inhibits growth of metastases and can be effectively combined with chemotherapy.

Background: scVEGF/(177)Lu is a novel radiopharmaceutical targeted by recombinant single-chain (sc) derivative of vascular endothelial growth factor (VEGF) that binds to and is internalized by vascular endothelial growth factor receptors (VEGFR). scVEGF/(177)Lu potential as adjuvant and neoadjuvant anti-angiogenic therapy was assessed in metastatic and orthotopic mouse models of triple-negative breast cancer.

Methods: Metastatic lesions in Balb/c mice were established by intracardiac injection of luciferase-expressing 4T1luc mouse breast carcinoma cells.

(99m)Tc-Annexin A5 quantification of apoptotic tumor response: a systematic review and meta-analysis of clinical imaging trials.

Purpose: (99m)Tc-Annexin A5 has been used as a molecular imaging probe for the visualization, characterization and measurement of apoptosis. In an effort to define the quantitative (99m)Tc-annexin A5 uptake criteria that best predict tumor response to treatment, we performed a systematic review and meta-analysis of the results of all clinical imaging trials found in the literature or publicly available databases.

Methods: Included in this review were 17 clinical trials investigating quantitative (99m)Tc-annexin A5 (qAnx5) imaging using different parameters in cancer patients before and after the first course of chemotherapy and/or radiation therapy.

[99mTc]Annexin V-128 SPECT Monitoring of Splenic and Disseminated Listeriosis in Mice: a Model of Imaging Sepsis.

Purpose: Here, we evaluate [(99m)Tc]annexin V-128, an in vivo marker of apoptosis, for single photon emission computed tomography (SPECT) imaging of localization and antibiotic treatment of disseminated bacterial infection, using a well-described mouse model that employs bioluminescent Listeria monocytogenes.

Procedures: Sixteen groups of five mice in six separate experiments were infected with bioluminescent Listeria, and in vivo bioluminescence imaging (BLI) was performed each day, to assess the location and extent of infection and response to antibiotics. [(99m)Tc]annexin V-128 was then injected for SPECT imaging, and the two sets of images were correlated and validated.

Ferumoxytol enhanced resting state fMRI and relative cerebral blood volume mapping in normal human brain.

The brain demonstrates spontaneous low-frequency (<0.1 Hz) cerebral blood flow (CBF) fluctuations, measurable by resting state functional MRI (rs-fMRI). Ultra small superparamagnetic iron oxide particles have been shown to enhance task-based fMRI signals (cerebral blood volume fMRI or CBV-fMRI), compared to the BOLD effect, by a factor of ≈2.

Attenuation of apoptosis by telmisartan in atherosclerotic plaques of apolipoprotein E-/- mice: evaluation using technetium 99m-annexin A5.

Technetium 99m (99mTc)-annexin A5, a marker of ongoing apoptosis, is supposed to be useful in the detection of metabolically active atheroma. The aim of this study was to determine the potential of 99mTc-annexin A5 for evaluating the therapeutic effects of an angiotensin II receptor type 1 blocker (ARB) (telmisartan) on atherosclerosis. Male apolipoprotein E-/- mice were divided into telmisartan-treated (3 mg/kg/d, n  =  10) and control (n  =  10) groups.

Synchrotron infrared imaging of advanced glycation endproducts (AGEs) in cardiac tissue from mice fed high glycemic diets.

Recent research findings correlate an increased risk for dieases such as diabetes, macular degeneration and cardiovascular disease (CVD) with diets that rapidly raise the blood sugar levels; these diets are known as high glycemic index (GI) diets which include white breads, sodas and sweet deserts. Lower glycemia diets are usually rich in fruits, non-starchy vegetables and whole grain products. The goal of our study was to compare and contrast the effects of a low vs.

Recent advances in the molecular imaging of programmed cell death: Part II--non-probe-based MRI, ultrasound, and optical clinical imaging techniques.

There is much that can be done to detect apoptosis and other forms of cell death with existing clinical modalities including ultrasound, MRI, and optical imaging without the need for current or new intravenous contrast agents. We will discuss how these widely available imaging technologies can readily be applied to the imaging of apoptosis in patients undergoing chemotherapy or radiation treatment. The limiting factor of course is the lack of knowledge of the optimal times after the start of treatment for the most accurate assessment of apoptosis and necrosis with each modality and specific technique.

Brain uptake of Tc99m-HMPAO correlates with clinical response to the novel redox modulating agent EPI-743 in patients with mitochondrial disease.

While decreased ATP production and redox imbalance are central to mitochondrial disease pathogenesis, efforts to develop effective treatments have been hampered by the lack of imaging markers of oxidative stress. In this study we wished to determine if Tc99m-HMPAO, a SPECT imaging marker of cerebral blood flow and glutathione/protein thiol content, could be used to monitor the effect(s) of EPI-743, an oral redox modulating, para-benzoquinone based therapeutic for mitochondrial disease. We hypothesized that treatment changes in HMPAO uptake would be inversely proportional to changes in oxidative stress within the brain and directly correlate to clinical response to EPI-743 therapy.

Recent advances in the molecular imaging of programmed cell death: part I--pathophysiology and radiotracers.

In humans, apoptosis (programmed cell death) is the most common form of cell death after necrosis. Apoptosis is a series of genetically preprogrammed biochemical and morphologic energy-requiring events that, after a specific external or internal stimulus, results in the physiologic disappearance of a cell via its self-disintegration and packaging of its contents into membrane vesicles called apoptotic bodies. Apoptotic bodies can readily be ingested, with their nutrients and even organelles recycled by neighboring cells or phagocytes without local inflammation.

Quantitative determination of apoptosis of pancreatic β-cells in a murine model of type 1 diabetes mellitus.

Unlabelled: Type 1 diabetes mellitus is characterized by a significant deficit in pancreatic β-cell mass, presumably caused by β-cell apoptosis. We investigated the incidence of β-cell apoptosis in streptozotocin-treated mice and nonobese diabetic (NOD) mice with (99m)Tc-annexin A5.

Methods: Vehicle-treated mice, streptozotocin-treated mice, and NOD mice at the ages of 5, 9, 16, and 20 wk (5-8 mice per group) were injected with (99m)Tc-annexin A5 and sacrificed 6 h later for autoradiography, and the regional (99m)Tc-annexin A5 level in the pancreas was evaluated.