Past and Present Scenario of Imaging Infection and Inflammation: A Nuclear Medicine Perspective

Nuclear medicine techniques provide potential non-invasive tools for imaging infections and inflammations in the body in a precise way. These techniques are further exploited by the use of radiopharmaceuticals in conjunction with imaging tests such as scintigraphy and positron emission tomography. Improved agents for targeting infection exploit the specific accumulation of radiolabeled compounds to understand the pathophysiologic changes involved in the inflammatory process and correlate them with other chronic illnesses. In the recent past, a wide variety of radiopharmaceuticals have been developed, broadly classified as specific radiopharmaceuticals and nonspecific radiopharmaceuticals. New developments in positron emission (leveraging 18 F and 18 fluorodeoxyglucose) and heterocyclic/peptide chemistry and radiochemistry are resulting in unique agents with high specific activity. Various approaches to visualizing infection and inflammation are presented in this review, in an integral manner, that give a clear view of the existing radiopharmaceuticals in clinical practice and those under development

Block Copolymer Based Nanoparticles for Theranostic Intervention of Cervical Cancer: Synthesis, Pharmacokinetics, and in Vitro/in Vivo Evaluation in HeLa Xenograft Models

Polymer-based nanoparticles have proven to be viable carriers of therapeutic agents. In this study, we have developed nanoparticles (NPs) from polypeptide-polyethylene glycol based triblock and diblock copolymers. The synthesized block copolymers poly­(ethylene glycol)-<i>b</i>-poly­(glutamic acid)-<i>b</i>-poly­(ethylene glycol) (GEG) and poly­(ethylene glycol)-<i>b</i>-poly­(glutamic acid) (EG) conjugated with folic acid for targeting specificity (EGFA) have been used to encapsulate methotrexate (MTX) to form M-GEG and M-EGFA NPs aimed at passive and active targeting of cervical carcinoma. In-vitro SRB cytotoxicity and hemolysis assays revealed that these NPs were cytocompatible to healthy human cells and hemocompatible to human RBCs. Cellular uptake by FACS demonstrated their prompt internalization by human cervical carcinoma (HeLa) cells and points toward an apoptotic mechanism of cell kill as confirmed by AO/EB staining as well as histological analysis of explanted HeLa tumors. Pharmacokinetics and biodistribution studies were performed in New Zealand albino rabbits and HeLa xenografted Athymic mice models, respectively, by radiolabeling these NPs with ^99mTc. Passive tumor accumulation and active targeting of MTX-loaded polymeric nanoparticles to folate expressing cells were confirmed by intravenous administration of these ^99mTc-labeled M-GEG and M-EGFA NPs in HeLa tumor bearing nude mice and clearly visualized by whole-body gamma-SPECT images of these mice. Survival studies of these xenografted mice established the antiproliferative effect of these MTX-loaded NPs while corroborating the targeting effect of folic acid. These studies proved that the M-GEG NPs and M-EGFA NPs could be effective alternatives to conventional chemotherapy along with simultaneous diagnostic abilities and thus potentially viable theranostic options for human cervical carcinoma

Past and Present Scenario of Imaging Infection and Inflammation: A Nuclear Medicine Perspective

Nuclear medicine techniques provide potential non-invasive tools for imaging infections and inflammations in the body in a precise way. These techniques are further exploited by the use of radiopharmaceuticals in conjunction with imaging tests such as scintigraphy and positron emission tomography. Improved agents for targeting infection exploit the specific accumulation of radiolabeled compounds to understand the pathophysiologic changes involved in the inflammatory process and correlate them with other chronic illnesses. In the recent past, a wide variety of radiopharmaceuticals have been developed, broadly classified as specific radiopharmaceuticals and nonspecific radiopharmaceuticals. New developments in positron emission (leveraging 18 F and 18 fluorodeoxyglucose) and heterocyclic/peptide chemistry and radiochemistry are resulting in unique agents with high specific activity. Various approaches to visualizing infection and inflammation are presented in this review, in an integral manner, that give a clear view of the existing radiopharmaceuticals in clinical practice and those under development

New developments in RiPP discovery, enzymology and engineering

Ribosomally-synthesized and post-translationally modified peptides (RiPPs) are a large group of natural products. A community-driven review in 2013 described the emerging commonalities in the biosynthesis of RiPPs and the opportunities they offered for bioengineering and genome mining. Since then, the field has seen tremendous advances in understanding of the mechanisms by which nature assembles these compounds, in engineering their biosynthetic machinery for a wide range of applications, and in the discovery of entirely new RiPP families using bioinformatic tools developed specifically for this compound class. The First International Conference on RiPPs was held in 2019, and the meeting participants assembled the current review describing new developments since 2013. The review discusses the new classes of RiPPs that have been discovered, the advances in our understanding of the installation of both primary and secondary post-translational modifications, and the mechanisms by which the enzymes recognize the leader peptides in their substrates. In addition, genome mining tools used for RiPP discovery are discussed as well as various strategies for RiPP engineering. An outlook section presents directions for future research

Management of coronary disease in patients with advanced kidney disease

BACKGROUND Clinical trials that have assessed the effect of revascularization in patients with stable coronary disease have routinely excluded those with advanced chronic kidney disease. METHODS We randomly assigned 777 patients with advanced kidney disease and moderate or severe ischemia on stress testing to be treated with an initial invasive strategy consisting of coronary angiography and revascularization (if appropriate) added to medical therapy or an initial conservative strategy consisting of medical therapy alone and angiography reserved for those in whom medical therapy had failed. The primary outcome was a composite of death or nonfatal myocardial infarction. A key secondary outcome was a composite of death, nonfatal myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. RESULTS At a median follow-up of 2.2 years, a primary outcome event had occurred in 123 patients in the invasive-strategy group and in 129 patients in the conservative-strategy group (estimated 3-year event rate, 36.4% vs. 36.7%; adjusted hazard ratio, 1.01; 95% confidence interval [CI], 0.79 to 1.29; P=0.95). Results for the key secondary outcome were similar (38.5% vs. 39.7%; hazard ratio, 1.01; 95% CI, 0.79 to 1.29). The invasive strategy was associated with a higher incidence of stroke than the conservative strategy (hazard ratio, 3.76; 95% CI, 1.52 to 9.32; P=0.004) and with a higher incidence of death or initiation of dialysis (hazard ratio, 1.48; 95% CI, 1.04 to 2.11; P=0.03). CONCLUSIONS Among patients with stable coronary disease, advanced chronic kidney disease, and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of death or nonfatal myocardial infarction

Health status after invasive or conservative care in coronary and advanced kidney disease

BACKGROUND In the ISCHEMIA-CKD trial, the primary analysis showed no significant difference in the risk of death or myocardial infarction with initial angiography and revascularization plus guideline-based medical therapy (invasive strategy) as compared with guideline-based medical therapy alone (conservative strategy) in participants with stable ischemic heart disease, moderate or severe ischemia, and advanced chronic kidney disease (an estimated glomerular filtration rate of &lt;30 ml per minute per 1.73 m2 or receipt of dialysis). A secondary objective of the trial was to assess angina-related health status. METHODS We assessed health status with the Seattle Angina Questionnaire (SAQ) before randomization and at 1.5, 3, and 6 months and every 6 months thereafter. The primary outcome of this analysis was the SAQ Summary score (ranging from 0 to 100, with higher scores indicating less frequent angina and better function and quality of life). Mixed-effects cumulative probability models within a Bayesian framework were used to estimate the treatment effect with the invasive strategy. RESULTS Health status was assessed in 705 of 777 participants. Nearly half the participants (49%) had had no angina during the month before randomization. At 3 months, the estimated mean difference between the invasive-strategy group and the conservative-strategy group in the SAQ Summary score was 2.1 points (95% credible interval, 120.4 to 4.6), a result that favored the invasive strategy. The mean difference in score at 3 months was largest among participants with daily or weekly angina at baseline (10.1 points; 95% credible interval, 0.0 to 19.9), smaller among those with monthly angina at baseline (2.2 points; 95% credible interval, 122.0 to 6.2), and nearly absent among those without angina at baseline (0.6 points; 95% credible interval, 121.9 to 3.3). By 6 months, the between-group difference in the overall trial population was attenuated (0.5 points; 95% credible interval, 122.2 to 3.4). CONCLUSIONS Participants with stable ischemic heart disease, moderate or severe ischemia, and advanced chronic kidney disease did not have substantial or sustained benefits with regard to angina-related health status with an initially invasive strategy as compared with a conservative strategy