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Date Added: Apr 26, 2021
Date Added: Apr 26, 2021
SARS-CoV-2 uses ACE2, an inhibitor of the Renin-Angiotensin-Aldosterone System (RAAS), for cellular entry. Studies indicate that RAAS imbalance worsens the prognosis in COVID-19. We present a consecutive retrospective COVID-19 cohort with findings of frequent pulmonary thromboembolism (17%), high pulmonary artery pressure (60%) and lung MRI perfusion disturbances. We demonstrate, in swine, that infusing angiotensin II or blocking ACE2 induces increased pulmonary artery pressure, reduces blood oxygenation, increases coagulation, disturbs lung perfusion, induces diffuse alveolar damage, and acute tubular necrosis compared to control animals. We further demonstrate that this imbalanced state can be ameliorated by infusion of an angiotensin receptor blocker and low-molecular-weight heparin. In this work, we show that a pathophysiological state in swine induced by RAAS imbalance shares several features with the clinical COVID-19 presentation. Therefore, we propose that severe COVID-19 could partially be driven by a RAAS imbalance.
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Date Added: Apr 26, 2021
Date Added: Apr 26, 2021
Vitamin D3 (cholecalciferol) is a secosteroid and prohormone which is metabolized in various tissues to the biologically most active vitamin D hormone 1,25(OH)2D3 (calcitriol). 1,25(OH)2D3 has multiple pleiotropic effects, particularly within the immune system, and is increasingly utilized not only within prophylaxis, but also within therapy of various diseases. In this context, the latest research has revealed clinical benefits of high dose vitamin D3 therapy in autoimmune diseases. The necessity of high doses of vitamin D3 for treatment success can be explained by the concept of an acquired form of vitamin D resistance. Its etiology is based on the one hand on polymorphisms within genes affecting the vitamin D system, causing susceptibility towards developing low vitamin D responsiveness and autoimmune diseases; on the other hand it is based on a blockade of vitamin D receptor signaling, e.g. through pathogen infections. In this paper, we review observational and mechanistic evidence for the acquired vitamin D resistance hypothesis. We particularly focus on its clinical confirmation from our experience of treating multiple sclerosis patients with the so-called Coimbra protocol, in which daily doses up to 1000 I.U. vitamin D3 per kg body weight can be administered safely. Parathyroid hormone levels in serum thereby provide the key information for finding the right dose. We argue that acquired vitamin D resistance provides a plausible pathomechanism for the development of autoimmune diseases, which could be treated using high-dose vitamin D3 therapy.
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3
Date Added: Apr 26, 2021
Authors: Markopoulou, Kalypso, et al
Date Added: Apr 26, 2021
Authors: Markopoulou, Kalypso, et al
Altered functioning of the hypothalamic-pituitary-adrenal (HPA) axis has been demonstrated in patients with treatment-resistant depression, although studies have often conflated patients with unipolar and bipolar depression. This is problematic given that the two groups often present with opposed neurovegetative symptom patterns. The aim of this study was to test, for the first time, whether post-awakening cortisol, a highly reliable, naturalistic measure of HPA functioning, could distinguish patients with clearly defined treatment-resistant unipolar (TRUD) and bipolar depression (TRBD). A total of 37 patients with TRUD, 17 patients with TRBD, and 47 healthy controls were recruited. Areas under the curve (AUC) with respect to the ground (g) and increase (i) of post-awakening cortisol concentrations (awakening, +15, +30, +45, +60, +90 min) were measured over two days. Patients with TRUD had higher total cortisol production in the morning hours compared to controls (AUCg, p = 0.01), while they did not differ in terms of the awakening response (AUCi, p = 0.28). By contrast, subjects with TRBD had lower total cortisol when compared to controls by trend (AUCg, p = 0.07), while they did not differ in the awakening response (AUCi, p = 0.15). A direct comparison of TRUD and TRBD revealed differences in the AUCg (p = 0.003) and AUCi (p = 0.03). This finding of comparatively elevated HPA axis activity in the morning in TRUD and attenuated HPA axis activity in TRBD attests to a fundamental biological distinction between unipolar and bipolar depression. It has implications for the understanding and treatment of bipolar depression and in differentiating the two types of depression.
99
Date Added: Mar 31, 2021
Date Added: Mar 31, 2021
99
Date Added: Mar 31, 2021
Date Added: Mar 31, 2021
83
Date Added: Mar 31, 2021
Date Added: Mar 31, 2021
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