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The semistable chelate manganese (Mn) dipyridoxyl diphosphate (MnDPDP, mangafodipir), previously used as an intravenous (i.v.) contrast agent (Teslascan™, GE Healthcare) for Mn-ion-enhanced MRI (MEMRI), should be reappraised for clinical use but now as a diagnostic drug with cytoprotective properties. Approved for imaging of the liver and pancreas, MnDPDP enhances contrast also in other targets such as the heart, kidney, glandular tissue, and potentially retina and brain. Transmetallation releases paramagnetic Mn 2+ for cellular uptake in competition with calcium (Ca 2+ ), and intracellular (IC) macromolecular Mn 2+ adducts lower myocardial T 1 to midway between native values and values obtained with gadolinium (Gd 3+ ). What is essential is that T 1 mapping and, to a lesser degree, T 1 weighted imaging enable quantification of viability at a cellular or even molecular level. IC Mn 2+ retention for hours provides delayed imaging as another advantage. Examples in humans include quantitative imaging of cardiomyocyte remodeling and of Ca 2+ channel activity, capabilities beyond the scope of Gd 3+ based or native MRI. In addition, MnDPDP and the metabolite Mn dipyridoxyl diethyl-diamine (MnPLED) act as catalytic antioxidants enabling prevention and treatment of oxidative stress caused by tissue injury and inflammation. Tested applications in humans include protection of normal cells during chemotherapy of cancer and, potentially, of ischemic tissues during reperfusion. Theragnostic use combining therapy with delayed imaging remains to be explored. This review updates MnDPDP and its clinical potential with emphasis on the working mode of an exquisite chelate in the diagnosis of heart disease and in the treatment of oxidative stress., Competing Interests: Jynge, Skjold, and Eidsaunet own shares in the Norwegian R&D company IC Targets AS that attempts to reintroduce MnDPDP for diagnostic use. Andersson and Karlsson own shares in the Swedish company PledPharma AB that promotes derivatives of MnDPDP for therapy. Jynge, Skjold, Andersson, and Karlsson are inventors of patents involving MnDPDP for diagnosis and/or therapy. Falkmer, Bruvold, Seland, and Blomlie declare no conflicts of interest., (Copyright © 2020 Per Jynge et al.)

Unlabelled: Quantitative imaging biomarkers could speed the development of new treatments for unmet medical needs and improve routine clinical care. However, it is not clear how the various regulatory and nonregulatory (eg, reimbursement) processes (often referred to as pathways) relate, nor is it clear which data need to be collected to support these different pathways most efficiently, given the time- and cost-intensive nature of doing so. The purpose of this article is to describe current thinking regarding these pathways emerging from diverse stakeholders interested and active in the definition, validation, and qualification of quantitative imaging biomarkers and to propose processes to facilitate the development and use of quantitative imaging biomarkers. A flexible framework is described that may be adapted for each imaging application, providing mechanisms that can be used to develop, assess, and evaluate relevant biomarkers. From this framework, processes can be mapped that would be applicable to both imaging product development and to quantitative imaging biomarker development aimed at increasing the effectiveness and availability of quantitative imaging., Supplemental Material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10100800/-/DC1., (RSNA, 2011)

A randomized double blind comparison of transdermal nitroglycerin and isosorbide dinitrate tablets was conducted in 100 men with stable angina pectoris. Subjective and objective effects were virtually identical for both regimens (number of angina attacks/nitroglycerin consumption and exercise ECG test variables). The pattern of side effects was also similar for both drugs. A considerable dissociation was observed between subjective effects and effects measured by ergometer test in the individual patient. Lack of both subjective and objective effects--i.e. nitrate tolerance--was observed in approximately one fourth of the patients, and was not prevented by a twelve-hour dosing interval on isosorbide dinitrate nor a six hour transdermal nitroglycerin-free interval. Our data lends credence to the notion that the effects of long-acting nitrates in daily life and the effects measured during stress testing may involve different mechanisms.

Rifampicin absorption was studied in six gastrectomized and six non-gastrectomized tuberculous patients who had been on continuous rifampicin therapy for more than 4 weeks. A dose of 450 mg was given on two occasions, first immediately after breakfast and, 2 days later, 1 h before breakfast. In all the gastrectomized and control patients a serum level well above the MIC for M. tuberculosis (0.2-0.5 microgram/ml) was achieved irrespective of whether rifampicin was administered after the meal or during fasting. Gastrectomized patients tended to have more delayed serum concentration peaks postprandially than when fasting. The differences in absorption were not statistically significant, and the serum concentrations remained above the MIC for M. tuberculosis for similar lenghts of time. Individual serum concentrations varied greatly, and this variation may represent a greater problem in the routine monitoring of rifampicin serum levels than administration of the drug with food.

The increases in medan scoresfluence on gastroduodenal mucosa of naproxen, 500 mg/day, and diclofenac, 100 mg/day, for 1 wk was investigated in 14 subjects in a double-blind randomized crossover study. Endoscopic examination of the gastroduodenal mucosa was carried out before and after each drug with regard to gastritis and hemorrhagic and erosive lesions. A 20-cm visual analogue scale was used for grading severity of mucosal changes. Naproxen caused statistically significant increases inmedian scores for all 3 variables, and 10 subjects showed a score increase in at least 1 variable; reaction to diclofenac occurred in only 4 subjects and the changes in median scores were not significant.

In a double-blind crossover study, the clinical anti-oedematous efficacy was compared of a weak cyclooxygenase inhibitor oxindanac 200 mg thrice daily in a controlled clinical trial procedure with paracetamol 1 g thrice daily as a positive control involving objective measurement of acute soft tissue oedema. Paracetamol is a weak cyclooxygenase inhibitor which reduces acute postoperative tissue oedema by 30% compared to a placebo. There was no significant (p = 0.81) difference between oxindanac and paracetamol with respect to anti-oedematous activity. The present finding is discussed in view of previous results obtained in controlled trials with several other anti-inflammatory drugs, using similar objective methodology as the present one. It is proposed that non-steroidal anti-inflammatory drugs acting solely by strong inhibition of cyclooxygenase need not be optimal anti-oedematous drugs. Reasons for this proposal are discussed.