Pure cerebellar ataxia due to bi-allelic PRDX3 variants including recurring p.Asp202Asn

Bi-allelic variants in peroxiredoxin 3 (PRDX3) have only recently been associated with autosomal recessive spinocerebellar ataxia characterized by early onset slowly progressive cerebellar ataxia, variably associated with hyperkinetic and hypokinetic features, accompanied by cerebellar atrophy and occasional olivary and brainstem involvement. Herein, we describe a further simplex case carrying a reported PRDX3 variant as well as two additional cases with novel variants. We report the first Brazilian patient with SCAR32, replicating the pathogenic status of a known variant. All presented cases from the Brazilian and Indian populations expand the phenotypic spectrum of the disease by displaying prominent neuroradiological findings. SCAR32, although rare, should be included in the differential diagnosis of sporadic or recessive childhood and adolescent-onset pure and complex cerebellar ataxia

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

Pharmacologic prophylaxis for atrial fibrillation following cardiac surgery: a systematic review

Atrial Fibrillation (AF) is the most common arrhythmia occurring after cardiac surgery. Its incidence varies depending on type of surgery. Postoperative AF may cause hemodynamic deterioration, predispose to stroke and increase mortality. Effective treatment for prophylaxis of postoperative AF is vital as reduces hospitalization and overall morbidity. Beta - blockers, have been proved to prevent effectively atrial fibrillation following cardiac surgery and should be routinely used if there are no contraindications. Sotalol may be more effective than standard b-blockers for the prevention of AF without causing an excess of side effects. Amiodarone is useful when beta-blocker therapy is not possible or as additional prophylaxis in high risk patients. Other agents such as magnesium, calcium channels blocker or non-antiarrhythmic drugs as glycose-insulin - potassium, non-steroidal anti-inflammatory drugs, corticosteroids, N-acetylcysteine and statins have been studied as alternative treatment for postoperative AF prophylaxis

Antiphospholipid syndrome; its implication in cardiovascular diseases: a review

Antiphospholipid syndrome (APLS) is a rare syndrome mainly characterized by several hyper-coagulable complications and therefore, implicated in the operated cardiac surgery patient. APLS comprises clinical features such as arterial or venous thromboses, valve disease, coronary artery disease, intracardiac thrombus formation, pulmonary hypertension and dilated cardiomyopathy. The most commonly affected valve is the mitral, followed by the aortic and tricuspid valve. For APLS diagnosis essential is the detection of so-called antiphospholipid antibodies (aPL) as anticardiolipin antibodies (aCL) or lupus anticoagulant (LA). Minor alterations in the anticoagulation, infection, and surgical stress may trigger widespread thrombosis. The incidence of thrombosis is highest during the following perioperative periods: preoperatively during the withdrawal of warfarin, postoperatively during the period of hypercoagulability despite warfarin or heparin therapy, or postoperatively before adequate anticoagulation achievement. Cardiac valvular pathology includes irregular thickening of the valve leaflets due to deposition of immune complexes that may lead to vegetations and valve dysfunction; a significant risk factor for stroke. Patients with APLS are at increased risk for thrombosis and adequate anticoagulation is of vital importance during cardiopulmonary bypass (CPB). A successful outcome requires multidisciplinary management in order to prevent thrombotic or bleeding complications and to manage perioperative anticoagulation. More work and reporting on anticoagulation management and adjuvant therapy in patients with APLS during extracorporeal circulation are necessary

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

Crocins: The active constituents of crocus sativus l. stigmas, exert significant cytotoxicity on tumor cells in vitro

Background: Tumors of the childhood are considered to be grave and devastating pa-thologies, with high mortality rates. Current therapeutic options like cytotoxic drugs and radiotherapy target both healthy and malignant cells, thus resulting in long-term neurological and intellectual sequelae and endocrinological disorders. Objectives: In this study, we focused on the anticancer potency of crocins, the main constituents of Crocus sativus L, stigmas. Crocins were first extracted using organic solvents from the dried stigmas and then were identified using the HPLC analysis. Materials and Methods: TE-671 cells were treated with the extract of crocins using a range of concentrations between 0.25-mg/ mL and 16 mg/mL. Viability of the cells was measured at 24h, 48h, 72h and 96h. In addition, we have examined the expression levels of the p53 gene using Real-Time Reverse Transcription PCR. Results: Results showed that crocins exerted significant cytotoxic and anti-proliferative effects in a concentration and time-dependent-manner on TE-671 cells. Furthermore, p53 manifested similar expression pattern as the anti-proliferative effect of crocin. Conclusion: Our data demonstrate that crocins could be a novel promising agent for the improvement of tumor treatment. © 2019 Bentham Science Publishers

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

Impact of 6 weeks of treatment with low-dose metformin and atorvastatin on glucose-induced changes of endothelial function in adults with newly diagnosed type 2 diabetes mellitus: A single-blind study.

BACKGROUND: Statin treatment has been reported to improve survival in patients with atherosclerosis, partly by improving vascular endothelial function. Elevation of blood glucose concentrations impairs endothelial function and promotes atherogenesis, but the effect of statins on glucose-induced endothelial dysfunction is unknown. Endothelium-dependent dilation (EDD) measured by gauge-strain plethysmography in the forearm is considered to be a reliable marker of endothelial function in forearm resistance vessels. OBJECTIVE: This study examined the combined effects of metformin and atorvastatin treatment on glucose-induced endothelial dysfunction (as EDD) in patients with newly diagnosed type 2 diabetes mellitus (DM). METHODS: Patients with newly diagnosed DM were recruited and were randomly assigned to receive metformin 850 mg/d or metformin 850 mg/d + atorvastatin 10 mg/d for 6 weeks in a single-blind study. All patients underwent glucose loading (75 g oral glucose after 12 hours of fasting) at baseline and at the end of the treatment period. Blood samples were obtained at baseline before glucose loading and 3 hours after loading to determine serum concentrations of cholesterol, lipoproteins, triglycerides, glucose, and glycosylated hemoglobin. EDD was evaluated at baseline and at 1, 2, and 3 hours after loading. The investigators were blinded to the treatment group assignments, and all analyses were performed in a blinded manner. Adverse events (eg, gastrointestinal disorders, myopathy, liver disorders) were monitored based on reported symptoms or signs (eg, myalgias, muscle cramps), clinical examination, and laboratory parameters (eg, increased liver and muscle enzymes). RESULTS: Thirty-two white patients with newly diagnosed type 2 DM were randomly assigned to receive metformin 850 mg/d (n = 17 [12 men]; mean [SD] age, 53.88 [45] years; body mass index [BMI], 28.7 [4.5] kg/m²) or metformin 850 mg/d + atorvastatin 10 mg/d (n = 15 [6 men]; mean age, 52.53 [37] years; BMI, 28.5 [2.1] kg/m²). At baseline, EDD was reduced 1 and 2 hours after glucose loading in both study groups (P < 0.01). Glucose loading was associated with an elevation of blood glucose concentrations at 1 and 2 hours (P < 0.01 vs resting levels before loading), and concentrations returned to resting levels at 3 hours, in both groups at baseline and after treatment. Metformin alone or in combination with atorvastatin was associated with a significant reduction in resting glucose concentrations after 6 weeks (both, P < 0.05 vs baseline), but only the combination of metformin + atorvastatin partly prevented the glucose-induced elevation of serum glucose at 1 hour after loading and the glucose-induced decrease in EDD (both, P < 0.01 vs baseline). CONCLUSIONS: Glucose loading blunted endothelial function, with a deterioration in EDD, in these patients with newly diagnosed type 2 DM. However, combined treatment with metformin and atorvastatin for 6 weeks partly prevented the glucose-induced impairment of EDD in these patients, with a significant difference compared with monotherapy with metformin

Interaction between cytokines and sCD40L in patients with stable and unstable coronary syndromes.

BACKGROUND: Evidence suggests that soluble CD40-ligand (sCD40L) is elevated in coronary artery disease (CAD) and is released from activated platelets during the acute myocardial infarction (AMI). Although sCD40L is part of immune response, the mechanisms regulating its release in different disease states remain unknown. MATERIALS AND METHODS: This study enrolled 596 subjects: 201 patients with stable CAD, 109 patients with AMI and 286 healthy controls. Circulating levels of sCD40L, interleukin-6 (IL-6), soluble vascular cell adhesion molecule-a (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1) were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Patients with AMI (n = 109) had higher levels of sCD40L and IL-6 compared to both CAD (n = 201) (P < 0.01) and controls (n = 286) (P < 0.01), while CAD also had higher levels of sCD40L and IL-6 compared to controls (P < 0.01). Similarly, sICAM-1 and sVCAM-1 levels were higher in CAD and AMI compared to controls (P < 0.05). IL-6 was the only parameter independently associated with sCD40L in healthy individuals [beta (SE):0.491(0.096), P = 0.0001]. However, in CAD or AMI, only diabetes mellitus [beta (SE): 2.689 (1.082), P = 0.044 and beta (SE): 10.406 (3.215), P = 0.002, respectively] and smoking [beta (SE): 3.470 (1.111), P = 0.002 and beta (SE): 9.694 (2.478), P = 0.0001, respectively] (but not IL-6), were independently associated with sCD40L levels. CONCLUSIONS: Both CAD and AMI are accompanied by increased levels of sCD40L in parallel with an elevation of proinflammatory cytokine IL-6 and adhesion molecules sVCAM-1 and sICAM-1. Diabetes mellitus and smoking (but not IL-6 or adhesion molecules) were the only factors independently associated with sCD40L levels in CAD and AMI patients