Acrylamide and Potential Risk of Diabetes Mellitus: Effects on Human Population, Glucose Metabolism and Beta-Cell Toxicity

Diabetes mellitus is a frequent endocrine disorder characterized by hyperglycemia. Acrylamide (AA) is food contaminant formed during the high-temperature processing of food rich in carbohydrates and low in proteins. Recent human epidemiological studies have shown a potential association between AA exposure and the prevalence of diabetes in the general population. In male rats, AA treatment promoted pancreatic islet remodeling, which was determined by alpha-cell expansion and beta-cell reduction, while in female rats AA caused hyperglycemia and histopathological changes in pancreatic islets. In vitro and in vivo rodent model systems have revealed that AA induces oxidative stress in beta cells and that AA impairs glucose metabolism and the insulin signaling pathway. Animal studies have shown that diabetic rodents are more sensitive to acrylamide and that AA aggravates the diabetic state. In this review, we provide an overview of human epidemiological studies that examined the relation between AA exposure and glucose disorders. In addition, the effects of AA treatment on pancreatic islet structure, beta-cell function and glucose metabolism in animal models are comprehensively analyzed with an emphasis on sex-related responses. Furthermore, oxidative stress as a putative mechanism of AA-induced toxicity in beta cells is explored. Finally, we discuss the effects of AA on diabetics in a rodent model system

Effect of Acrylamide Treatment on Cyp2e1 Expression and Redox Status in Rat Hepatocytes

Acrylamide (AA) toxicity is associated with oxidative stress. During detoxification, AA is either coupled to gluthatione or biotransformed to glycidamide by the enzyme cytochrome P450 2E1 (CYP2E1). The aim of our study was to examine the hepatotoxicity of AA in vivo and in vitro. Thirty male Wistar rats were treated with 25 or 50 mg/kg b.w. of AA for 3 weeks. Qualitative and quantitative immunohistochemical evaluation of inducible nitric oxide synthase (iNOS), CYP2E1, catalase (CAT), superoxide dismutase 1 (SOD1), and SOD2 expression in liver was carried out. Bearing in mind that the liver is consisted mainly of hepatocytes, in a parallel study, we used the rat hepatoma cell line H4IIE to investigate the effects of AA at IC20 and IC50 concentrations on the redox status and the activity of CAT, SOD, and glutathione-S-transferase (GST), their gene expression, and CYP2E1 and iNOS expression. Immunohistochemically stained liver sections showed that treatment with AA25mg induced a significant decrease of CYP2E1 protein expression (p 50mg led to a significant increase of iNOS protein expression (p p 50mg (p p > 0.05). In AA-treated H4IIE cells, a concentration-dependent significant increase in lipid peroxidation and nitrite levels was observed (p p 50 significantly enhanced GST activity (p p 50 significantly increased the transcription of SOD1, GSTA2, and GSTP1 genes (p 20 significantly decreased mRNA for CYP2E1 in H4IIE cells (p < 0.05). Obtained results indicate that AA treatments, both in vivo and in vitro, change hepatocytes; drug-metabolizing potential and disturb its redox status

In-Hospital Mortality of COVID-19 Patients Treated with High-Flow Nasal Oxygen: Evaluation of Biomarkers and Development of the Novel Risk Score Model CROW-65

To replace mechanical ventilation (MV), which represents the cornerstone therapy in severe COVID-19 cases, high-flow nasal oxygen (HFNO) therapy has recently emerged as a less-invasive therapeutic possibility for those patients. Respecting the risk of MV delay as a result of HFNO use, we aimed to evaluate which parameters could determine the risk of in-hospital mortality in HFNO-treated COVID-19 patients. This single-center cohort study included 102 COVID-19-positive patients treated with HFNO. Standard therapeutic methods and up-to-date protocols were used. Patients who underwent a fatal event (41.2%) were significantly older, mostly male patients, and had higher comorbidity burdens measured by CCI. In a univariate analysis, older age, shorter HFNO duration, ventilator initiation, higher CCI and lower ROX index all emerged as significant predictors of adverse events (p &lt; 0.05). Variables were dichotomized and included in the multivariate analysis to define their relative weights in the computed risk score model. Based on this, a risk score model for the prediction of in-hospital mortality in COVID-19 patients treated with HFNO consisting of four variables was defined: CCI &gt; 4, ROX index ≤ 4.11, LDH-to-WBC ratio, age &gt; 65 years (CROW-65). The main purpose of CROW-65 is to address whether HFNO should be initiated in the subgroup of patients with a high risk of in-hospital mortality

Acute Arterial Thrombosis of Lower Extremities in COVID-19 Patients

Clinical signs and symptoms of COVID-19 varied from asymptomatic forms to severe, life-threatening conditions that required treatment in intensive care units. These severe forms of illness are connected with a hypercoagulable state due to excessive inflammation, hypoxia, immobilisation, and altered angiotensin-converting enzyme 2 (ACE-2). In total, 17 COVID-19 positive patients were diagnosed with peripheral arterial thrombosis (AT), 13 of them had COVID-19 pneumonia. Laboratory findings in patients with X-ray confirmed pneumonia showed a four times higher neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP) and three times higher lactate dehydrogenase level (LDH) than patients without confirmed pneumonia. Patients with pneumonia had significantly more bilateral occlusions of the lower extremities and a significantly higher percentage with complete occlusion of the arteries than patients without pneumonia. The rate of limb loss was 35.3%. They were all from the group with COVID-19 pneumonia. Ten out of thirteen patients with pneumonia died due to acute respiratory distress syndrome (ARDS). All patients without pneumonia were discharged from the hospital. The aim of this retrospective study was to report the incidence of arterial thrombosis of lower extremities and their complications in the acute phase of the infection among COVID-19 patients admitted to the hospital for treatment