Cardiac surgery (CS) with extracorporeal circulation (ECC), induces intense oxidative stress (OS) and systemic inflammatory response (SIR), which may seriously affect postoperative lung function. We ...aimed to test if high parenteral (200 mg/kg/24 h) daily doses of Vitamin C (VitC), given within 48 h after the beginning of the operation, may reduce the incidence and severity of postoperative pulmonary complications (PPCs) in CS patients. This single-center, prospective, randomized, single-blinded, interventional trial included 150 patients, assigned to control Group A (
= 75) and interventional Group B (
= 75). Group B intraoperatively received one-fourth (i.e., 50 mg/kg) of the planned daily Vit C dose, divided into three equal parts and diluted in 10 mL of normal saline, while Group A received an equal volume of normal saline at the same time frames (i.e., the induction of anesthesia, aortic cross-clamp release, and sternal closure). After 6 h from the first intraoperative dose, the following regimen was applied: Group B: 50 mg/kg, 30 min i.v. infusion of VitC in 50 mL of normal saline, every 6 h, for the next 48 h, and Group A: 30 min i.v. infusion of an equal volume of normal saline every 6 h, for the next 48 h. Modified Kroenke's score was used to determine the incidence and severity of PPCs. The overall incidence of PPCs was 36.7% and was significantly lower in Group B (13.3% vs. 60.0%,
< 0.001). The PPCs severity score was also significantly lower in Group B (1 vs. 3,
< 0.001). In addition, patients from Group B had significantly less damaged lungs, better postoperative renal function, shorter ICU stays, fewer ICU re-admissions, and lower hospital mortality. No VitC-related adverse effects were recorded. High parenteral daily VitC doses given within 48 h after the beginning of CS are safe and effective in reducing the incidence and severity of PPCs. A multicenter RCT is needed to confirm these results.
Based on considerable interest to enlarge the experimental database of radioresistant cells after their irradiation with helium ions, HTB140, MCF-7 and HTB177 human malignant cells are exposed to ...helium ion beams having different linear energy transfer (LET).PURPOSEBased on considerable interest to enlarge the experimental database of radioresistant cells after their irradiation with helium ions, HTB140, MCF-7 and HTB177 human malignant cells are exposed to helium ion beams having different linear energy transfer (LET).The cells are irradiated along the widened 62 MeV/u helium ion Bragg peak, providing LET of 4.9, 9.8, 23.4 and 36.8 keV/µm. Numerical simulations with the Geant4 toolkit are used for the experimental design. Cell survival is evaluated and compared with reference γ-rays. DNA double strand breaks are assessed via γ-H2AX foci.MATERIALS AND METHODSThe cells are irradiated along the widened 62 MeV/u helium ion Bragg peak, providing LET of 4.9, 9.8, 23.4 and 36.8 keV/µm. Numerical simulations with the Geant4 toolkit are used for the experimental design. Cell survival is evaluated and compared with reference γ-rays. DNA double strand breaks are assessed via γ-H2AX foci.With the increase of LET, surviving fractions at 2 Gy decrease, while RBE (2 Gy, γ) gradually increase. For HTB140 cells, above the dose of 4 Gy, a slight saturation of survival is observed while the increase of RBE (2 Gy, γ) remains unaffected. With the increase of LET the increase of γ-H2AX foci is revealed at 0.5 h after irradiation. There is no significant difference in the number of foci between the cell lines for the same LET. From 0.5 to 24 h, the number of foci drops reaching its residual level. For each time point, there are small differences in DNA DSB among the three cell lines.RESULTSWith the increase of LET, surviving fractions at 2 Gy decrease, while RBE (2 Gy, γ) gradually increase. For HTB140 cells, above the dose of 4 Gy, a slight saturation of survival is observed while the increase of RBE (2 Gy, γ) remains unaffected. With the increase of LET the increase of γ-H2AX foci is revealed at 0.5 h after irradiation. There is no significant difference in the number of foci between the cell lines for the same LET. From 0.5 to 24 h, the number of foci drops reaching its residual level. For each time point, there are small differences in DNA DSB among the three cell lines.Analyses of data acquired for the three cell lines irradiated by helium ions, having different LET, reveal high elimination capacity and creation of a large number of DNA DSB with respect to γ-rays, and are between those reported for protons and carbon ions.CONCLUSIONAnalyses of data acquired for the three cell lines irradiated by helium ions, having different LET, reveal high elimination capacity and creation of a large number of DNA DSB with respect to γ-rays, and are between those reported for protons and carbon ions.
Introduction Cisplatin is one of the most frequently used chemotherapeutics, which is known to cause both tumor and normal lung tissue damage through the generation of free radicals and cells ...apoptosis/necrosis. Melatonin is a neurohormone that regulates numerous physiological processes in the body both through receptor pathways and by maintaining tissue redox homeostasis. Material and methods The extent of rat lung damage induced by cisplatin and the effects of melatonin on this process was determined based on the pathohistological changes and biochemical disturbances in tissue lipid peroxidation, protein carbonyl modification and in the activity of xanthine oxidase (XO), caspase-3 and DNases. Results Histopathological analysis of rat lung tissue obtained from animals that received cisplatin found them to be edematous, with significant deterioration of alveolar epithelium. These morphological changes are accompanied by a significant increase in all studied oxidative stress-related parameters, as well as with the activity of apoptosis-related enzymes. A five-day treatment with melatonin completely prevented a cisplatin-induced increase in oxidative stress-related parameters and in the activity of XO, caspase-3 and alkaline DNase. Also, the histopathological changes observed during microscopic analysis were much less pronounced than in the group that received cisplatin only. Conclusions These results can potentially be connected with the ability of melatonin to inhibit the activity of XO, caspase-3 and alkaline DNase and/or its ability to scavenge free radicals, thus preventing lung damage induced by cisplatin.
Many available SARS-CoV-2 vaccines demonstrated good humoral response, but studies directly comparing their immunogenicity in the general population are lacking. We evaluated the medium−term kinetics ...of anti-S SARS-CoV-2 antibodies (Abs) at one and six months after the second dose of BNT162b2, BBIBP-CorV, and Gam-COVID-Vac. Immunogenicity at six months was directly compared between BNT162b2, BBIBP-CorV, Gam-COVID-Vac, and ChAdOx1 nCoV-19. Participants ≥ 20 years old from Novi Sad, Serbia, without prior SARS-CoV-2 infection, were included. Anti S1/S2 IgG antibodies were measured using quantitative LIAISON SARS-CoV-2 assay. A total of 368 participants were included: 231 (62.77%) had sera collected at two time points. Two doses of BNT162b2 were received by 37.50% of participants, followed by BBIBP-CorV (22.01%), Gam-COVID-Vac (21.47%), and ChAdOx1 nCoV-19 (19.02%). Mean Ab levels at the 28th day and 6 months were 216.55 (SD = 105.73) AU/mL and 75.68 (SD = 57.30) for BNT162b2, 194.38 (SD = 140.24) and 90.53 (SD = 111.30) for Gam-COVID-Vac, and 72.74 (SD = 80.04) and 24.43 (SD = 38.43) for BBIBP-CorV group (p < 0.01, between two time points across all three groups), with a significant difference between women and men (p < 0.01, for both sexes). At the sixth month post-vaccination, the highest mean Ab level was detected in Gam-COVID-Vac group (91.28 AU/mL, SD = 95.96), followed by BNT162b2 (85.25 AU/mL, SD = 60.02), ChAdOx1 nCoV-19 (64.22 AU/mL, SD = 65.30), and BBIBP-CorV (25.26 AU/mL, SD = 36.92) (p < 0.01). Anti-spike IgG persistence was demonstrated six months post-vaccination with a significant decline in Ab levels. These results suggest a lower protection against SARS-CoV-2 over time. Our findings support the introduction of additional (booster) doses.
Many articles in the literature deal with horseradish peroxidase (HRP) biomineralization, but none pay attention to the isoenzyme composition of commercial HRP or the influence of the carbohydrate ...component of the protein molecule on the biomineralization process. To study the impact of these factors, we performed periodate oxidation of commercial HRP and a purified HRP-C isoform for biomineralization within ZIF-8. With purified HRP, enzyme@ZIF-8 biocomposites with higher activity were obtained, while periodate oxidation of the carbohydrate component of both commercial HRP and purified HRP-C yields biocomposites with very high activity in acetate buffer that does not degrade the ZIF-8 structure. Using acetate instead of phosphate buffer can prevent the false high activity of HRP@ZIF-8 biocomposites caused by the degradation of ZIF-8 coating. At the same time, purification and especially oxidation of the carbohydrate component of enzymes prior to biomineralization lead to significantly improved activity of the biocomposites.
Healthcare workers (HCWs) are a vulnerable and critical population in the ongoing response to the SARS-CoV-2 pandemic. We aimed to estimate the seroprevalence in HCWs considering all of their ...previous contacts with the SARS-CoV-2 virus and/or the immunity acquired through their immunization against COVID-19 before the advent of the Omicron variants BA.4/BA.5. Serum samples were collected from 28 March to 10 June 2022. We covered 25% out of all the people who worked in some of the government healthcare centers (primary, secondary, and tertiary level) across the entire Autonomous Province of Vojvodina (Northern Serbia). Two serological tests (Anti-SARS-CoV-2 QuantiVac ELISA and LIAISON® SARS-CoV-2 TrimericS) were used to detect anti-spike IgG antibodies. The overall prevalence of the SARS-CoV-2 antibody among the 6936 HCWs was 92.96% 95% CI 92.33−93.55. Regarding the type of serological test, there was a statistically significant (p = 0.0079) difference of the seropositivity obtained by the LIAISON® SARS-CoV-2 TrimericS (93.87%, 95% CI 92.97−94.69) and Anti-SARS-CoV-2 QuantiVac ELISA (92.23%, 95% CI 91.34−93.06) tests. Seropositivity to SARS-CoV-2 significantly (p < 0.0001) increased with the number of SARS-CoV-2 infections combined with the number of doses of the SARS-CoV-2 vaccines received. A vast majority of the HCWs in Vojvodina had detectable levels of antibodies to the spike protein of SARS-CoV-2, but despite this high seropositivity, it is unknown whether this herd immunity among HCWs is protective against the new variants of concern. Further research should evaluate the rates of reinfections and the associated severity of COVID-19 caused by the Omicron sublineages and/or new variants of SARS-CoV-2 among HCWs.
Introduction
Disruption of copper homeostasis and dysfunction of mitochondria have been documented in sclerotic hippocampi (HS) of patients with mesial temporal lobe epilepsy (mTLE). However, a ...potential link between these pathological changes has not been tackled so far. Herein, we analyzed regional distribution of neuron somata density, copper concentration, and the activity of cytochrome c oxidase (CCO), a component of mitochondrial electron transport chain and copper‐containing metalloprotein, in HS.
Methods
Histochemical staining and laser ablation inductively coupled plasma mass spectrometry were carried out to construct comparable maps of these parameters in coronal sections of hippocampi of 3 mTLE‐HS patients and 3 control subjects.
Results
Copper levels were decreased in all regions of HS with pyramidal neuron somata. CCO activity was significantly reduced in stratum pyramidale (PY) 1 and cornu Ammonis field 4, the two regions with significant reduction in neuron somata density. CCO activity was also lower in layers that contain apical dendrites of pyramidal neurons and mossy fibers. It appears that copper deficiency in PY2 and PY3 comes before CCO activity reduction and neuronal loss. A strong positive correlation was found between neuron density, Cu concentration, and CCO activity.
Conclusions
Presented results imply that pathological alterations in Cu and energy metabolism could be involved in the development of HS. A limitation of this study was the relatively small number of patients. However, presented results underline copper deficiency as a component of pathological mechanisms of epilepsy and warrant further investigation of cuproproteins and members of copper transport machinery.
Regional distribution of neuron somata density, copper concentration, and the activity of cytochrome c oxidase in coronal sections of sclerotic hippocampi of epilepsy patients and controls.
Tryptophan (TRP) catabolites exert neuroactive effects, with the plethora of evidence suggesting that kynurenic acid (KYNA), a catabolite of the kynurenine pathway (KP), acts as the regulator of ...glutamate and acetylcholine in the brain, contributing to the schizophrenia pathophysiology. Newer evidence regarding measures of KP metabolites in the blood of schizophrenia patients and from the central nervous system suggest that blood levels of these metabolites by no means could reflect pathological changes of TRP degradation in the brain. The aim of this study was to investigate plasma concentrations of TRP, kynurenine (KYN) and KYNA at the acute phase and remission of schizophrenia in a prospective, case-control study of highly selected and matched schizophrenia patients and healthy individuals. Our study revealed significantly decreased KYN and KYNA in schizophrenia patients (
< 0.001), irrespective of illness state, type of antipsychotic treatment, number of episodes or illness duration and no differences in the KYN/TRP ratio between schizophrenia patients and healthy individuals. These findings could be interpreted as indices that kynurenine pathway might not be dysregulated in the periphery and that other factors contribute to observed disturbances in concentrations, but as our study had certain limitations, we cannot draw definite conclusions. Further studies, especially those exploring other body compartments that participate in kynurenine pathway, are needed.
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