Evaluation of Possible Association between Serum Levels of Aldosterone and Cortisol with Clinical Symptoms Progression in COVID-19 Suspicious Outpatients Tested for SARS-CoV2 RT-PCR: An Analytical Cross-Sectional Study.

Aldosterone is a key component of Renin-Angiotensin-Aldosterone System (RAAS). The RAAS could play a substantial role in the pathophysiology of coronavirus disease 2019 (COVID-19). Moreover, the dynamics of the Hypothalamic-Pituitary-Adrenal (HPA) axis may have changed in COVID-19. Cortisol, as an important factor in assessing immune system activity, is an important part of this axis. The present study compared the serum levels of aldosterone and cortisol in COVID-19 outpatients with those of potentially non-infected participants. It was also aimed to assess the possible association between serum levels of aldosterone and cortisol with clinical symptoms progression in COVID-19 outpatients. Demographic characteristics (i.e., gender and age) and clinical data (i.e., oxygen saturation [SPO2], respiratory rate [RR], and heart rate) were collected. Serum cortisol and aldosterone measurements were conducted using the ELISA technique. Clinical symptoms of the positive polymerase chain reaction (PCR) group were followed up on for 28 days in weekly intervals. SPO2 was significantly lower in the positive PCR group; however, the RR was significantly higher (P=0.03 and P=0.001, respectively). Significantly higher levels of aldosterone were found in males of the negative PCR group, compared to females (P=0.05). Cortisol (OR=0.937, P=0.033) and aldosterone (OR=1.005, P=0.020) levels had a decreasing and increasing effect on the chances of respiratory symptoms occurring over time, respectively. Furthermore, over time, women were twice as likely as men to develop neurologic symptoms (OR=0.530, P=0.015). According to the findings of this study, cortisol and aldosterone are associated with the chance of respiratory symptoms occurring over time. However, the levels of these two markers do not seem to be related to the progression of clinical symptoms of lower grades of COVID-19.

Erythropoietin attenuates experimental haemorrhagic shock-induced renal damage through an iNOS- dependent mechanism in male Wistar rats.

AIM: Erythropoietin (EPO) is shown to exert protective effects on different tissues in haemorrhagic shock (HS) states. Nitric oxide (NO), as a multifunctional signaling molecule, is implicated in diverse physiologic and pathologic processes. In order to understand the exact mechanism of EPO protection, in this study we evaluated the role of different NOS enzymes in the EPO signaling pathway in male rats. METHODS: Rats were randomized to five groups: 1) Sham, 2) HS 3) EPO 4) L-NAME, a non-specific NOS inhibitor 5) 1400W, a specific iNOS inhibitor. HS was induced by withdrawal of 50% of total blood volume. After 2h, resuscitation was performed with the shed blood and Ringer's lactate. In group 3, rats were treated with EPO (300IU/kg, i.v.) over 10min before HS induction. In the L-NAME and 1400W groups, L-NAME (10mg/kg, i.p.) and 1400W (2mg/kg, i.p.) were administered 30min before EPO injection. Blood and kidney tissue samples were obtained 3h after resuscitation. RESULTS: EPO increased the survival rate and significantly improved kidney function and histology compared to the HS group. There were less renal oxidative stress, apoptosis and systemic inflammatory responses in the EPO group. EPO increased eNOS and more abundantly iNOS mRNA expressions. L-NAME and 1400W significantly abolished all beneficial effects of EPO. CONCLUSION: In this in vivo animal model, we showed that EPO administration prior to HS attenuates renal injury and dysfunction in rats. The protective effects of EPO may be mediated by nitric oxide and the expression of different NOS enzymes, especially iNOS isoform.

Inhibition of breast tumor growth and abnormal angiogenesis in mice treated with endothelial cells and their progenitor mesenchymal stem cells derived from bone marrow.

Incorporation of endothelial cells or their progenitor cells into newly sprouting blood vessels can contribute to tissue vascularization after ischemic injury. However, the interaction of the stem cells-derived endothelial cells with angiogenesis within tumors is not well understood. The aim of this study was to examine the efficiency of endothelial-like cells derived from MSCs in controlling breast tumor growth associated with abnormal angiogenesis. For this purpose, Balb/c mouse model of breast carcinoma was developed and subjected to intra tumor (I.T)/intra venous (I.V) therapy with undifferentiated MSCs or endothelial cells derived from them. The homing of the stem cells was approved by measuring different markers as well as tracing green fluorescence protein (GFP)-labeled MSCs in the tumors. Tumor growth was measured following cell therapy using a digital caliper. At the end of treatment period (30 days) the angiogenesis markers; VEGFR2 expression as well as micro-vessel density (MVD) using CD31 were estimated in tumor tissues. Stem cell transplantation to mice bearing breast tumors resulted in tumor growth suppression in all experimental groups. The endothelial markers; CD31 and VEGFR2 were down regulated following I.T delivery of the endothelial cells. Accordingly, angiogenesis was suppressed following I.T administration of endothelial cells which was associated with increased focal necrosis in the tumors. In conclusion, data show that endothelial cells directly injected into tumors is more efficient compared to undifferentiated MSCs in controlling tumor-associated angiogenesis and tumor growth.