Covid-19 disease, women’s predominant non-heparin vaccine-induced thrombotic thrombocytopenia and kounis syndrome: A passepartout cytokine storm interplay

Coronavirus disease 2019 (COVID-19) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) constitute one of the deadliest pandemics in modern history demonstrating cardiovascular, gastrointestinal, hematologic, mucocutaneous, respiratory, neurological, renal and testicular manifestations and further complications. COVID-19-induced excessive immune response accompanied with uncontrolled release of cytokines culminating in cytokine storm seem to be the common pathogenetic mechanism of these complications. The aim of this narrative review is to elucidate the relation between anaphylaxis associated with profound hypotension or hypoxemia with pro-inflammatory cytokine release. COVID-19 relation with Kounis syndrome and post-COVID-19 vaccination correlation with heparin-induced thrombocytopenia with thrombosis (HITT), especially serious cerebral venous sinus thrombosis, were also reviewed. Methods: A current literature search in PubMed, Embase and Google databases was performed to reveal the pathophysiology, prevalence, clinical manifestation, correlation and treatment of COVID-19, anaphylaxis with profuse hypotension, Kounis acute coronary syndrome and thrombotic events post vaccination. Results: The same key immunological pathophysiology mechanisms and cells seem to underlie COVID-19 cardiovascular complications and the anaphylaxis-associated Kounis syndrome. The myocardial injury in patients with COVID-19 has been attributed to coronary spasm, plaque rupture and microthrombi formation, hypoxic injury or cytokine storm disposing the same pathophysiology with the three clinical variants of Kounis syndrome. COVID-19-interrelated vaccine excipients as polysorbate, polyethelene glycol (PEG) and trometamol constitute potential allergenic substances. Conclusion: Better acknowledgement of the pathophysiological mechanisms, clinical similarities, multiorgan complications of COVID-19 or other viral infections as dengue and human immunodeficiency viruses along with the action of inflammatory cells inducing the Kounis syndrome could identify better immunological approaches for prevention, treatment of the COVID-19 pandemic as well as post-COVID-19 vaccine adverse reactions

Relationship between mean blood glucose and glycated haemoglobin in Type 2 diabetic patients

Aims: To correlate the values of MBG to HbA1c in Greek patients with Type 2 diabetes and/or metabolic syndrome. Methods: We followed up 140 Greek adult patients: 92 patients with Type 2 diabetes treated with insulin or oral glucose-lowering medication, and 48 patients with newly diagnosed Type 2 diabetes or metabolic syndrome not receiving any treatment. MBG was calculated for each patient from self-measurements of blood glucose using a portable glucometer, made six times a day (before eating and 2 h after a meal), three times a week for 1 month. HbA1c was determined by HPLC at 0 and 12 weeks. Results: HbA1c at 0 (x) and 12 weeks (y) correlated strongly (y = 0.790x + 1.115, r = 0.92), confirming that the patient's glycaemic status remained stable during the whole period of follow-up. Linear regression was performed on MBG values; HbA1c at 12 weeks, sex, age, body mass index (BMI) and patient status (Type 2 diabetes treated or not) were used as independent variables. None of the independent variables reached statistical significance in the model, with the exception of HbA1c at 12 weeks. The final model was: MBG (mg/dl) = (34.74 × HbA1c) - 79.21, r = 0.93; or MBG (mmol/l) = 1.91 × HbA1c - 4.36, r = 0.93. Conclusions: Our results establish for the first time a strong correlation between MBG and HbA1c in Type 2 diabetic patients and support the idea of expressing HbA1c results as MBG. This will help patients to gain a clearer interpretation of the result, with less confusion. This simplification will allow every person with diabetes using home glucose-monitoring to understand his or her own target level. © 2008 The Authors

Untargeted plasma metabolomics unravels a metabolic signature for tissue sensitivity to glucocorticoids in healthy subjects: Its implications in dietary planning for a healthy lifestyle

In clinical practice, differences in glucocorticoid sensitivity among healthy subjects may influence the outcome and any adverse effects of glucocorticoid therapy. Thus, a fast and accurate methodology that could enable the classification of individuals based on their tissue glucocorticoid sensitivity would be of value. We investigated the usefulness of untargeted plasma metabolomics in identifying a panel of metabolites to distinguish glucocorticoid-resistant from glucocorticoid-sensitive healthy subjects who do not carry mutations in the human glucocorticoid receptor (NR3C1) gene. Applying a published methodology designed for the study of glucocorticoid sensitivity in healthy adults, 101 healthy subjects were ranked according to their tissue glucocorticoid sensitivity based on 8:00 a.m. serum cortisol concentrations following a very low-dose dexamethasone suppression test. Ten percent of the cohort, i.e., 11 participants, on each side of the ranking, with no NR3C1 mutations or polymorphisms, were selected, respectively, as the most glucocorticoid-sensitive and most glucocorticoid-resistant of the cohort to be analyzed and compared with untargeted blood plasma metabolomics using gas chromatography–mass spectrometry (GC–MS). The acquired metabolic profiles were evaluated using multivariate statistical analysis methods. Nineteen metabolites were identified with significantly lower abundance in the most sensitive compared to the most resistant group of the cohort, including fatty acids, sugar alcohols, and serine/threonine metabolism inter-mediates. These results, combined with a higher glucose, sorbitol, and lactate abundance, suggest a higher Cori cycle, polyol pathway, and inter-tissue one-carbon metabolism rate and a lower fat mobilization rate at the fasting state in the most sensitive compared to the most resistant group. In fact, this was the first study correlating tissue glucocorticoid sensitivity with serine/threonine metabolism. Overall, the observed metabolic signature in this cohort implies a worse cardiometabolic profile in the most glucocorticoid-sensitive compared to the most glucocorticoid-resistant healthy subjects. These findings offer a metabolic signature that distinguishes most glucocorticoid-sensitive from most glucocorticoid-resistant healthy subjects to be further validated in larger cohorts. More-over, they support the correlation of tissue glucocorticoid sensitivity with insulin resistance and metabolic syndrome-associated pathways, further emphasizing the need for nutritionists and doctors to consider the tissue glucocorticoid sensitivity in dietary and exercise planning, particularly when these subjects are to be treated with glucocorticoids. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Untargeted Plasma Metabolomics Unravels a Metabolic Signature for Tissue Sensitivity to Glucocorticoids in Healthy Subjects: Its Implications in Dietary Planning for a Healthy Lifestyle

In clinical practice, differences in glucocorticoid sensitivity among healthy subjects may influence the outcome and any adverse effects of glucocorticoid therapy. Thus, a fast and accurate methodology that could enable the classification of individuals based on their tissue glucocorticoid sensitivity would be of value. We investigated the usefulness of untargeted plasma metabolomics in identifying a panel of metabolites to distinguish glucocorticoid-resistant from glucocorticoid-sensitive healthy subjects who do not carry mutations in the human glucocorticoid receptor (NR3C1) gene. Applying a published methodology designed for the study of glucocorticoid sensitivity in healthy adults, 101 healthy subjects were ranked according to their tissue glucocorticoid sensitivity based on 8:00 a.m. serum cortisol concentrations following a very low-dose dexamethasone suppression test. Ten percent of the cohort, i.e., 11 participants, on each side of the ranking, with no NR3C1 mutations or polymorphisms, were selected, respectively, as the most glucocorticoid-sensitive and most glucocorticoid-resistant of the cohort to be analyzed and compared with untargeted blood plasma metabolomics using gas chromatography–mass spectrometry (GC–MS). The acquired metabolic profiles were evaluated using multivariate statistical analysis methods. Nineteen metabolites were identified with significantly lower abundance in the most sensitive compared to the most resistant group of the cohort, including fatty acids, sugar alcohols, and serine/threonine metabolism intermediates. These results, combined with a higher glucose, sorbitol, and lactate abundance, suggest a higher Cori cycle, polyol pathway, and inter-tissue one-carbon metabolism rate and a lower fat mobilization rate at the fasting state in the most sensitive compared to the most resistant group. In fact, this was the first study correlating tissue glucocorticoid sensitivity with serine/threonine metabolism. Overall, the observed metabolic signature in this cohort implies a worse cardiometabolic profile in the most glucocorticoid-sensitive compared to the most glucocorticoid-resistant healthy subjects. These findings offer a metabolic signature that distinguishes most glucocorticoid-sensitive from most glucocorticoid-resistant healthy subjects to be further validated in larger cohorts. Moreover, they support the correlation of tissue glucocorticoid sensitivity with insulin resistance and metabolic syndrome-associated pathways, further emphasizing the need for nutritionists and doctors to consider the tissue glucocorticoid sensitivity in dietary and exercise planning, particularly when these subjects are to be treated with glucocorticoids

Anticoagulation for atrial fibrillation in heart failure patients: Balancing between Scylla and Charybdis

The management of heart failure (HF) and atrial fibrillation (AF) in real-world practice remains a debating issue, while the number of HF patients with AF increase dramatically. While it is unclear if rhythm or rate control therapy is more beneficial and under which circumstances, anticoagulation therapy is the cornerstone of the AF-HF patients' approach. Vitamin-K antagonists were the gold-standard during the past, but currently their usage is limited in specific conditions. Non-vitamin K oral anticoagulants (NOACs) have gained ground during the last ten years and considered as gold-standard of a wide spectrum of HF phenotypes. The current manuscript aims to review the current literature regarding the indications and the optimal choice and usage of NOACs in HF patients with AF. © 2021 JGC All rights reserved; www.jgc301.co

Biophysical Studies and In Vitro Effects of Tumor Cell Lines of Cannabidiol and Its Cyclodextrin Inclusion Complexes

Phytocannabinoids possess anticancer properties, as established in vitro and in vivo. However, they are characterized by high lipophilicity. To improve the properties of cannabidiol (CBD), such as solubility, stability, and bioavailability, CBD inclusion complexes with cyclodextrins (CDs) might be employed, offering targeted, faster, and prolonged CBD release. The aim of the present study is to investigate the in vitro effects of CBD and its inclusion complexes in randomly methylated β-CD (RM-β-CD) and 2-hyroxypropyl-β-CD (HP-β-CD). The enhanced solubility of CBD upon complexation with CDs was examined by phase solubility study, and the structure of the inclusion complexes of CBD in 2,6-di-O-methyl-β-CD (DM-β-CD) and 2,3,6-tri-O-methyl-β-CD (TM-β-CD) was determined by X-ray crystallography. The structural investigation was complemented by molecular dynamics simulations. The cytotoxicity of CBD and its complexes with RM-β-CD and HP-β-CD was tested on two cell lines, the A172 glioblastoma and TE671 rhabdomyosarcoma cell lines. Methylated β-CDs exhibited the best inclusion ability for CBD. A dose-dependent effect of CBD on both cancer cell lines and improved efficacy of the CBD–CDs complexes were verified. Thus, cannabinoids may be considered in future clinical trials beyond their palliative use as possible inhibitors of cancer growth

Biophysical Studies and In Vitro Effects of Tumor Cell Lines of Cannabidiol and Its Cyclodextrin Inclusion Complexes

Phytocannabinoids possess anticancer properties, as established in vitro and in vivo. However, they are characterized by high lipophilicity. To improve the properties of cannabidiol (CBD), such as solubility, stability, and bioavailability, CBD inclusion complexes with cyclodextrins (CDs) might be employed, offering targeted, faster, and prolonged CBD release. The aim of the present study is to investigate the in vitro effects of CBD and its inclusion complexes in randomly methylated β-CD (RM-β-CD) and 2-hyroxypropyl-β-CD (HP-β-CD). The enhanced solubility of CBD upon complexation with CDs was examined by phase solubility study, and the structure of the inclusion complexes of CBD in 2,6-di-O-methyl-β-CD (DM-β-CD) and 2,3,6-tri-O-methyl-β-CD (TM-β-CD) was determined by X-ray crystallography. The structural investigation was complemented by molecular dynamics simulations. The cytotoxicity of CBD and its complexes with RM-β-CD and HP-β-CD was tested on two cell lines, the A172 glioblastoma and TE671 rhabdomyosarcoma cell lines. Methylated β-CDs exhibited the best inclusion ability for CBD. A dose-dependent effect of CBD on both cancer cell lines and improved efficacy of the CBD–CDs complexes were verified. Thus, cannabinoids may be considered in future clinical trials beyond their palliative use as possible inhibitors of cancer growth

CGRP and migraine from a cardiovascular point of view: What do we expect from blocking CGRP?

Calcitonin gene-related peptide (CGRP) is a neuropeptide with a pivotal role in the pathophysiology of migraine. Blockade of CGRP is a new therapeutic target for patients with migraine. CGRP and its receptors are distributed not only in the central and peripheral nervous system but also in the cardiovascular system, both in blood vessels and in the heart. We reviewed the current evidence on the role of CGRP in the cardiovascular system in order to understand the possible short- and long-term effect of CGRP blockade with monoclonal antibodies in migraineurs. In physiological conditions, CGRP has important vasodilating effects and is thought to protect organs from ischemia. Despite the aforementioned cardiovascular implication, preventive treatment with CGRP antibodies has shown no relevant cardiovascular side effects. Results from long-term trials and from real life are now needed. © 2019 The Author(s)