Maternal Serum Copper and Some Metabolic Indexes in Late Second Trimester of Gestational Diabetes Mellitus Pregnancy.

BACKGROUND: Copper (Cu) is a physiologically important trace element during pregnancy. The study aim is to assess the altered level of serum Cu and its association with some metabolic indexes in Gestational Diabetes Mellitus (GDM). METHODS: A total of 108 pregnant women (aged 18 - 40, second trimester) are included in the study and divided into two groups (GDM n = 54; pregnant with normal glucose tolerance (NGT), n = 54) after performing a 2-hour 75-g oral glucose tolerance test (OGTT). Maternal blood samples are collected at 26 - 28 gestational week. All biochemical parameters are measured in serum from fasting venous blood. Serum Cu levels are analyzed by flame atomic absorption spectrophotometry (Perkin Elmer AAnalyst 300, USA). Body Mass Index (BMI), insulin sensitivity/resistance, triglyceride-glucose (TyG), TyG-BMI (triglyceride glucose-body mass) indexes are calculated by formulas. RESULTS: The following data were observed: significantly higher levels of serum Cu (p = 0.009), pre-pregnancy BMI (pre-pBMI), BMI at the GDM diagnosis (pBMI), TyG, pregnancy TyG-BMI (pTyG-BMI) p < 0.001, and triglycerides (Tgl) (p = 0.02) in GDM compared to NGT pregnancy. The study presents a positive correlation between serum Cu and pre-pBMI (p < 0.02), pBMI and pTyG-BMI (p < 0.001). Besides, pre-pBMI (mean ≥ 25 kg/m2), pBMI (mean ≥ 30 kg/m2), and pTyG-BMI are associated with 14.5% (OR 1.145, 95% CI: 1.064 - 1.232; p < 0.001), 15.3% (OR 1.153, 95% CI: 1.070 - 1.243; p < 0.001), and 5.9% (OR 1.059, 95% CI: 1.022 - 1.086; p < 0.001) increased risk for GDM development. No association is found between Cu and Tgl levels, fasting plasma glucose e(FPG) and TyG. ROC analysis suggests the serum Cu as a possible risk factor for GDM development. The analysis shows that at a cutoff point of ≥ 31.9 µmol/L, serum Cu presents a sensitivity and specificity of 64.8% and 66.7% in the prediction of GDM development (AUC = 0.659, p < 0.012). After adjustment for maternal age, gestational age, and family predisposition, the odds ratios (ORs) (95% CIs) still show association of Cu levels with increased GDM risk (OR 1.099, 95% CI 1.018 - 1.184, p = 0.013). CONCLUSIONS: pTyG-BMI index exhibits a better interaction than TyG index, Tgl, and glucose separately with serum Cu levels where BMI has a mediator's role.

Progressive volume reduction and long-term aneurysmal collapse following flow diversion treatment of giant and symptomatic cerebral aneurysms.

Background: The primary goal of conventional endovascular and microvascular approaches is the clinical and radiological resolution of the symptomatic aneurysm-induced mass effect. This study assessed the volume changes and mass effect reduction due to sac shrinkage after treatment with flow diverter stents (FD) for unruptured cerebral aneurysms. Methods: We analyzed retrospectively 36 symptomatic aneurysms that were larger or equal to 25 mm in diameter in patients treated at our center from January 2016 to April 2022. Radiological and clinical outcomes were analyzed, including aneurysmal volume changes and resolution of aneurysm-related symptoms. Results: At 6 months, 25 aneurysms decreased in size, 2 remained unchanged, and 9 aneurysms demonstrated a post-treatment dimensional increase. At 12 months, 30 aneurysms showed a progressive radiological volume reduction. Either no change or negligible shrinkage was observed in the remaining six aneurysms. At 24 months, 32 aneurysms showed aneurysmal shrinkage by a mean 47% volume loss with respect to baseline. At the last follow-up, all 13 patients who had presented with third cranial nerve palsy showed improvements. Complete reversal of the pretreatment edematous changes was confirmed in all cases. The overall post-treatment complication rate was 8.3%, as 3 patients experienced non-fatal delayed rupture of their aneurysm. There was no mortality in this study. Conclusion: Flow diversion could effectively induce progressive aneurysmal shrinkage and resolution of the mass effect associated with giant symptomatic cerebral aneurysms.

Fibroblast Growth Factor 21 as a Marker of Prediabetes in Patients with Non-alcoholic Fatty Liver Disease.

BACKGROUND: Fibroblast growth factor 21 is a peptide primarily secreted by the liver in response to peroxisome proliferator-activated receptor-α activation which plays an important role in regulating carbohydrate and lipid metabolism. This study investigated the association between fibroblast growth factor 21 and prediabetes in obese patients with non-alcoholic fatty liver disease in adult population. METHODS: A total of 85 obese non-alcoholic fatty liver disease patients without (n = 49) and with prediabetes (n = 36) were included. Serum fibroblast growth factor 21 levels were determined by enzyme-linked immunosorbent assay. RESULTS: Higher fibroblast growth factor 21 serum levels were observed in patients with prediabetes, metabolic syndrome, dyslipidemia, and insulin resistance. There were significant correlations between fibroblast growth factor 21 and waist-to-stature ratio, visceral adiposity index, triglycerides, very low-density lipoproteins, alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), Quantitative Insulin Sensitivity Check Index, and Stumvoll index of insulin sensitivity. Fibroblast growth factor 21 level ≥320 pg/mL was associated with a 4.2-fold higher risk of prediabetes and ≥270 pg/mL for metabolic syndrome approximately 4 times. CONCLUSION: Fibroblast growth factor 21 is associated with increased risk for prediabetes, metabolic syndrome, and insulin resistance in obese patients with non-alcoholic fatty liver disease.

Evaluation of zinc, copper, and Cu:Zn ratio in serum, and their implications in the course of COVID-19.

BACKGROUND: The dynamics of essential metals such as Copper (Cu) and Zinc (Zn) may be associated with the novel coronavirus disease 2019 (COVID-19) that has spread across the globe. OBJECTIVES: The aim of this study is to investigate the relationship between serum levels of Cu and Zn, as well as the Cu:Zn ratio in the acute phase of COVID-19 along with the assessment of their connection to other laboratory parameters (hematological, biochemical, hemostatic). METHODS: Serum levels of Cu and Zn were measured by atomic absorption spectrometry in 75 patients in the acute COVID-19 phase and were compared with those of 22 COVID-19 patients evaluated three months after the acute phase of the disease ('non-acute' group) and with those of 68 healthy individuals. RESULTS: In comparison with both the non-acute patients and the healthy controls, the acute patients had lower levels of hemoglobulin and albumin, and higher levels of glucose, creatinine, liver transaminases, C-reactive protein (CRP), and higher values of the neutrophils to lymphocytes ratio (NLR) at the hospital admission. They also exhibited increased levels of Cu and decreased of Zn, well represented by the Cu:Zn ratio which was higher in the acute patients than in both non-acute patients (p = 0.001) and healthy controls (p < 0.001), with no statistical difference between the last two groups. The Cu:Zn ratio (log scale) positively correlated with CRP (log scale; r = 0.581, p < 0.001) and NLR (r = 0.436, p = 0.003). CONCLUSION: Current results demonstrate that abnormal dynamics of Cu and Zn levels in serum occur early during the course of COVID-19 disease, and are mainly associated with the inflammation response.

Interferon-gamma release assays outcomes in healthy subjects following BNT162b2 mRNA COVID-19 vaccination.

The pathogenesis of COVID-19 involves both humoral and cellular immunological responses, with cell-mediated immunity being discussed as the primary and most effective immune response to viral infection. It is supposed that COVID-19 vaccines also elicited effective cell immune response, and specifically IFNγ secreted by SARS-CoV-2-specific T-helper 1 and Tcytotoxic cells. Using an interferon-gamma release assay (IGRA) test, we aimed to monitor cellular post-vaccination immunity in healthy subjects vaccinated with BNT162b2 mRNA COVID-19 vaccine (Comirnaty). We tested 37 healthcare workers (mean age 54.3 years, range 28-72, 22 females, 15 males) following COVID-19 mRNA COVID-19 vaccine and 15 healthy unvaccinated native persons as control subjects using QuantiFERON SARS-CoV-2 RUO test, performed approximately 1 month after vaccination. We also measured virus-neutralizing antibodies. Thirty-one out of 37 tested subjects had significantly raised levels of SARS-CoV-2 specific IFNγ against SARS-CoV-2 Ag1 and Ag2 1 month following COVID-19 vaccination. In addition, we found a significant difference between the IFNγ levels in fully vaccinated subjects and the control group (p < 0.01).We also found a substantial correlation (r = 0.9; p < 0.01) between virus-neutralizing antibodies titers and IFNγ concentrations released by T cells. We believe that IGRA tests are an excellent tool to assess the development of a post-vaccination immune response when immunized against SARS-CoV-2. However, IGRA-based tests should be performed within a few weeks following vaccination. Therefore, we can speculate that the application of these tests to assess long-term immune response is debatable.

Increased Serum Pentraxin 3 Is Associated with Prediabetes and Type 2 Diabetes in Obese Patients with Nonalcoholic Fatty Liver Disease.

Background: Pentraxin 3 (PTX3) is an acute-phase protein, which resembles C-reactive protein in both structure and function, and belongs to the same family. PTX3 is associated with cardiovascular diseases, obesity, and metabolic syndrome (MetS). This study evaluated the relationship between serum PTX3 levels, prediabetes, newly diagnosed type 2 diabetes mellitus (T2DM), and other biochemical and clinical parameters in obese patients with nonalcoholic fatty liver disease (NAFLD). Methods: A total of 77 obese patients with NAFLD were included. Forty-seven of them were with normal glucose levels and 30 were with glycemic disorders, including prediabetes and newly diagnosed T2DM. Serum PTX3 was measured using ELISA method. Results: Higher PTX3 serum levels were found in patients with prediabetes and T2DM compared with those with normal blood glucose (2321.29 ± 926.63 vs. 1877.03 ± 895.45 pg/mL, P = 0.028). There were significant correlations between PTX3 and alanine aminotransferase (P = 0.018), gamma-glutamyl transferase (P = 0.005), and neuropathy disability score (P < 0.05). The presence of hypertension, dyslipidemia, insulin resistance, and MetS, as well as the number of components of the MetS did not affect PTX3 levels. Conclusions: PTX3 serum levels were higher in an obese subject with NAFLD with prediabetes and T2DM.

PNPLA3 I148M Polymorphism in Patients with Nonalcoholic Fatty Liver Disease, Obesity and Prediabetes.

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) is closely associated with obesity and insulin resistance, and therefore predisposes to type 2 diabetes and cardiovascular diseases. Lipid deposition in the liver seems to be critical in the pathogenesis of NAFLD. A common genetic variant, the patatin-like phospholipase domain-containing protein 3 (PNPLA3) has been associated with NAFLD. The aim of the present study was to evaluate the association between PNPLA3, key gene of lipid metabolism and the metabolic traits in obesity NAFLD patients with and without prediabetes. METHODS: A total of 208 obese NAFLD patients without (n=125) and with prediabetes (n=83) were included. The genotyping of PNPLA3 I148M variant (rs738409) was performed by restriction analysis. RESULTS: Regarding rs738409 (I148M) polymorphism, CG genotype was positively correlated with prediabetes, insulin resistance, dyslipidemia and metabolic syndrome compared to the wild CC genotype. The carriers of the PNPLA3 I148M variant have 9.6-fold higher risk of glucose disturbances compared to wild genotype (OR 9.649, 95%CI 2.100-44.328, р=0.004). The carriers of the PNPLA3 I148M variant also have a 3 times higher risk for the presence of metabolic syndrome (OR 2.939, 95% CI: 1.590-5.434, p=0.001) and a 2.1-fold higher risk for the presence of insulin resistance (OR 2.127, 95% CI: 1.078-4.194, p=0.029). CONCLUSIONS: PNPLA3 I148M is associated with increased risk of prediabetes, metabolic syndrome and insulin resistance in obese patients with NAFLD.

Copper dyshomeostasis in Wilson disease and Alzheimer's disease as shown by serum and urine copper indicators.

Abnormal handling of copper is the cause of Wilson disease (WD), a rare disorder typified by increased levels in plasma copper not-bound to ceruloplasmin (nCp-Cu, also known as 'free' copper). In Alzheimer's disease (AD), meta-analyses show that copper decreases in brain but increases in serum, due to the nCp Cu component increase. Despite the similarities, a direct comparison of copper biological status in the two diseases has never been carried out. To fill this gap, we evaluated serum copper, ceruloplasmin, nCp-Cu and Cu:Cp in 385 CE and 336 healthy controls previously investigated that were compared with 9 newly diagnosed WD patients. We then assessed 24h copper urinary excretion in 24 WD patients under D-penicillamine (D-pen) treatment and in 35 healthy controls, and compared results with those of AD patients participating to a D-pen phase II clinical trial previously published. After adjusting for sex and age, serum nCp-Cu and Cu:Cp resulted higher in AD and in WD than in healthy controls (both p<0.001). While nCp-Cu was similar between AD and WD, Cu:Cp was higher in WD (p<0.016). 24h urinary copper excretion in AD patients (12.05µg/day) was higher than in healthy controls (4.82µg/day; p<0.001). 77.8% of the AD patients under D-pen treatment had a 24h urinary excretion higher than 200µg/day, suggestive of a failure of copper control. This study provides new insight into the pathophysiology of copper homeostasis in AD, showing a failure of copper control and the Cu:Cp ratio as an eligible marker.

Fluorescent substituted amidines of benzanthrone: synthesis, spectroscopy and quantum chemical calculations.

Several new substituted amidine derivatives of benzanthrone were synthesized by a condensation reaction from 3-aminobenzo[de]anthracen-7-one and appropriate aromatic and aliphatic amides. The obtained derivatives have a bright yellow or orange fluorescence in organic solvents and in solid state. The novel benzanthrone derivatives were characterized by TLC analysis, (1)H NMR, IR, MS, UV/vis, and fluorescence spectroscopy. The solvent effect on photophysical behaviors of these dyes was investigated, and the results showed that the Stoke's shift increased, whereas quantum yield decreased with the growth of the solvent polarity. The structure of some dyes was confirmed by the X-ray single crystal structure analysis. AM1, ZINDO/S and ab initio calculations using Gaussian software were carried out to estimate the electron system of structures. The calculations show planar configurations for the aromatic core of these compounds and two possible orientations of amidine substituents. The calculation results correlate well with red-shifted absorption and emission spectra of compounds.