The angiotensin type 2 receptor (AT2R) and the receptor Mas are components of the protective arms of the renin-angiotensin system (RAS), i.e. they both mediate tissue protective and regenerative actions. The spectrum of actions of these two receptors and their signalling mechanisms display striking similarities. Moreover, in some instances, antagonists for one receptor are able to inhibit the action of agonists for the respective other receptor. These observations suggest that there may be a functional or even physical interaction of both receptors. This article discusses potential mechanisms underlying the phenomenon of blockade of angiotensin-(1-7) [Ang-(1-7)] actions by AT2R antagonists and vice versa. Such mechanisms may comprise dimerization of the receptors or dimerization-independent mechanisms such as lack of specificity of the receptor ligands used in the experiments or involvement of the Ang-(1-7) metabolite alamandine and its receptor MrgD in the observed effects. We conclude that evidence for a functional interaction of both receptors is strong, but that such an interaction may be species- and/or tissue-specific and that elucidation of the precise nature of the interaction is only at the very beginning.
Differentiating between glioblastomas and solitary brain metastases proves to be a challenging diagnosis for neuroradiologists, as both present with imaging patterns consisting of peritumoral hyperintensities with similar intratumoral texture on traditional magnetic resonance imaging sequences. Early diagnosis is paramount, as each pathology has completely different methods of clinical assessment. In the past decade, recent developments in advanced imaging modalities enabled providers to acquire a more accurate diagnosis earlier in the patient’s clinical assessment, thus optimizing clinical outcome. Dynamic susceptibility contrast has been optimized for detecting relative cerebral blood flow and relative cerebral blood volume. Diffusion tensor imaging can be used to detect changes in mean diffusivity. Neurite orientation dispersion and density imaging is an innovative modality detecting changes in intracellular volume fraction, isotropic volume fraction, and extracellular volume fraction. Magnetic resonance spectroscopy is able to assist by providing a metabolic descriptor while detecting variable ratios of choline/N-acetylaspartate, choline/creatine, and N-acetylaspartate/creatine. Finally, radiomics and machine learning algorithms have been devised to assist in improving diagnostic accuracy while often utilizing more than one advanced imaging protocol per patient. In this review, we provide an update on all the current evidence regarding the identification and differentiation of glioblastomas from solitary brain metastases.
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