scholarly journals Structural and Functional Characteristics of the Liver Under the Effect of Different Doses of Sodium Tetraborate

2019 ◽  
Vol 8 (1) ◽  
pp. 31-38
Author(s):  
A. K. Berdalinova ◽  
T. Zh. Umbetov ◽  
N. N. Shevlyuk ◽  
G. A. Zhurabekova
Keyword(s):  
Prolonged Exposure ◽  
Sodium Tetraborate ◽  
Functional Characteristics ◽  
Functional Changes ◽  
Cell Structures ◽  
Adaptive Capabilities ◽  
Low Concentrations ◽  
Destructive Processes ◽  
Blood Elements

The aim of the study was to clarify the morphological and functional changes in the liver under the effect of sodium tetraborate.Material and methods. Morphological and functional characteristics of the liver of white outbred rats under single and long-term exposure to sodium tetraborate were studied using histological, histochemical, immunocytochemical and morphometric methods. Experimental animals were divided into 2 groups. Animals of the first group once intragastrically administered sodium tetraborate at a dose of LD50, animals of the second group daily for a month administered sodium tetraborate at a dose of 1/10 LD50. Animals of the first group were removed from the experiment a day after the introduction of sodium tetraborate, animals of the second group – 7, 14, 21 and 30 days after the start of the experiment.Results. Both single and long-term exposure to sodium tetraborate in the liver lobules marked multiple focal death of hepatocytes, microcirculation, bile stagnation in the biliary tract. The degree of damage and death of hepatocytes increases from the periphery to the center of the lobule. With prolonged exposure to sodium tetraborate in the first half of the experiment, stagnation of the blood elements in the capillaries was rare, and with an increase in the duration of the experiment (from 7 to 30 days), the proportion of intra-lobular sinusoid capillaries with stagnation of the shaped elements in them increased and more than half of the capillaries showed stagnation of the blood elements in them. Destructive changes in the liver were more pronounced when exposed to sodium tetraborate at a dose of LD50.Conclusion. In the conditions of low concentrations of sodium tetraborate in the liver, both destructive processes and transformations aimed at compensating for damage occur. With an increase in the dose of sodium tetraborate, the adaptive capabilities of the organ are exhausted and do not compensate for the damage to the cell structures of the organ.

The Neurobiology of Pain

2019 ◽  
pp. 387-414
Author(s):  
Maria Fitzgerald ◽  
Michael W. Salter
Keyword(s):  
Early Life ◽  
Pain Perception ◽  
Long Term Effects ◽  
Male And Female ◽  
Functional Changes ◽  
Pain Pathways ◽  
Developmental Age ◽  
Short And Long Term ◽  
Age And Sex

The influence of development and sex on pain perception has long been recognized but only recently has it become clear that this is due to specific differences in underlying pain neurobiology. This chapter summarizes the evidence for mechanistic differences in male and female pain biology and for functional changes in pain pathways through infancy, adolescence, and adulthood. It describes how both developmental age and sex determine peripheral nociception, spinal and brainstem processing, brain networks, and neuroimmune pathways in pain. Finally, the chapter discusses emerging evidence for interactions between sex and development and the importance of sex in the short- and long-term effects of early life pain.

scholarly journals The Role of Cell Metabolism in Innate Immune Memory

2020 ◽  
pp. 1-9
Author(s):  
Anaisa Valido Ferreira ◽  
Jorge Domiguéz-Andrés ◽  
Mihai Gheorghe Netea
Keyword(s):  
Metabolic Pathways ◽  
Tricarboxylic Acid Cycle ◽  
Cell Metabolism ◽  
Innate Immune ◽  
Immune Memory ◽  
Functional Changes ◽  
Trained Immunity ◽  
Health And Disease

Immunological memory is classically attributed to adaptive immune responses, but recent studies have shown that challenged innate immune cells can display long-term functional changes that increase nonspecific responsiveness to subsequent infections. This phenomenon, coined <i>trained immunity</i> or <i>innate immune memory</i>, is based on the epigenetic reprogramming and the rewiring of intracellular metabolic pathways. Here, we review the different metabolic pathways that are modulated in trained immunity. Glycolysis, oxidative phosphorylation, the tricarboxylic acid cycle, amino acid, and lipid metabolism are interplaying pathways that are crucial for the establishment of innate immune memory. Unraveling this metabolic wiring allows for a better understanding of innate immune contribution to health and disease. These insights may open avenues for the development of future therapies that aim to harness or dampen the power of the innate immune response.

scholarly journals Screening for Effects of Inhaled Nanoparticles in Cell Culture Models for Prolonged Exposure

Nanomaterials ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 606
Author(s):  
Claudia Meindl ◽  
Kristin Öhlinger ◽  
Verena Zrim ◽  
Thomas Steinkogler ◽  
Eleonore Fröhlich
Keyword(s):  
Prolonged Exposure ◽  
A549 Cells ◽  
Cytokine Release ◽  
Transient Effects ◽  
Particle Uptake ◽  
Particle Accumulation ◽  
Low Concentrations ◽  
Culture Models ◽  
20 Nm ◽  
Inhaled Nanoparticles

Respiratory exposure of humans to environmental and therapeutic nanoparticles repeatedly occurs at relatively low concentrations. To identify adverse effects of particle accumulation under realistic conditions, monocultures of Calu-3 and A549 cells and co-cultures of A549 and THP-1 macrophages in the air–liquid interphase culture were exposed repeatedly to 2 µg/cm2 20 nm and 200 nm polystyrene particles with different functionalization. Particle accumulation, transepithelial electrical resistance, dextran (3–70 kDa) uptake and proinflammatory cytokine secretion were determined over 28 days. Calu-3 cells showed constant particle uptake without any change in barrier function and cytokine release. A549 cells preferentially ingested amino- and not-functionalized particles combined with decreased endocytosis. Cytokine release was transiently increased upon exposure to all particles. Carboxyl-functionalized demonstrated higher uptake and higher cytokine release than the other particles in the A549/THP-1 co-cultures. The evaluated respiratory cells and co-cultures ingested different amounts and types of particles and caused small (partly transient) effects. The data suggest that the healthy cells can adapt to low doses of non-cytotoxic particles.

scholarly journals Impact of Prolonged Exposure of Eleven Years to Hot Seawater on the Degradation of a Thermoset Composite

Polymers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 2154
Author(s):  
Amir Hussain Idrisi ◽  
Abdel-Hamid I. Mourad ◽  
Muhammad M. Sherif
Keyword(s):  
Exposure Time ◽  
Prolonged Exposure ◽  
Mechanical Performance ◽  
Matrix Cracking ◽  
Pull Out ◽  
Strength Based ◽  
Different Temperatures ◽  
River Line ◽  
Composite Samples

This paper presents a long-term experimental investigation of E-glass/epoxy composites’ durability exposed to seawater at different temperatures. The thermoset composite samples were exposed to 23 °C, 45 °C and 65 °C seawater for a prolonged exposure time of 11 years. The mechanical performance as a function of exposure time was evaluated and a strength-based technique was used to assess the durability of the composites. The experimental results revealed that the tensile strength of E-glass/epoxy composite was reduced by 8.2%, 29.7%, and 54.4% after immersion in seawater for 11 years at 23 °C, 45 °C, and 65 °C, respectively. The prolonged immersion in seawater resulted in the plasticization and swelling in the composite. This accelerated the rate of debonding between the fibers and matrix. The failure analysis was conducted to investigate the failure mode of the samples. SEM micrographs illustrated a correlation between the fiber/matrix debonding, potholing, fiber pull-out, river line marks and matrix cracking with deterioration in the tensile characteristics of the thermoset composite.

scholarly journals Continuous Long-Term Exposure to Low Concentrations of MWCNTs Induces an Epithelial-Mesenchymal Transition in BEAS-2B Cells

Nanomaterials ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1742
Author(s):  
Hélène Barthel ◽  
Christian Darne ◽  
Laurent Gaté ◽  
Athanase Visvikis ◽  
Carole Seidel
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Pulmonary Exposure ◽  
Adverse Health Effects ◽  
Low Concentrations ◽  
Mitotic Abnormalities ◽  
Epithelial Marker ◽  
Multi Walled Carbon Nanotubes ◽  
Walled Carbon Nanotubes

In the field of nanotechnology, the use of multi-walled carbon nanotubes (MWCNTs) is growing. Pulmonary exposure during their production, use, and handling is raising concerns about their potential adverse health effects. The purpose of this study is to assess how the physical characteristics of MWCNTs, such as diameter and/or length, can play a role in cellular toxicity. Our experimental design is based on the treatment of human bronchial epithelial cells (BEAS-2B) for six weeks with low concentrations (0.125–1 µg/cm2) of MWCNTs having opposite characteristics: NM-403 and Mitsui-7. Following treatment with both MWCNTs, we observed an increase in mitotic abnormalities and micronucleus-positive cells. The cytotoxic effect was delayed in cells treated with NM-403 compared to Mitsui-7. After 4–6 weeks of treatment, a clear cellular morphological change from epithelial to fibroblast-like phenotype was noted, together with a change in the cell population composition. BEAS-2B cells underwent a conversion from the epithelial to mesenchymal state as we observed a decrease in the epithelial marker E-cadherin and an increased expression of mesenchymal markers N-cadherin, Vimentin, and Fibronectin. After four weeks of recovery, we showed that the induced epithelial-mesenchymal transition is reversible, and that the degree of reversibility depends on the MWCNT.

scholarly journals Onset and Resolution of Key Adverse Events in Valbenazine-Treated Patients with Tardive Dyskinesia: Pooled Analyses from Two Long-Term Clinical Trials

CNS Spectrums ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 151-151
Author(s):  
Stephen R. Marder ◽  
Jean-Pierre Lindenmayer ◽  
Chirag Shah ◽  
Tara Carmack ◽  
Angel S. Angelov ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Tardive Dyskinesia ◽  
Suicidal Behavior ◽  
Prolonged Exposure ◽  
First Occurrence ◽  
Balance Disorder ◽  
Clinical Interest ◽  
Post Hoc

AbstractObjectiveTardive dyskinesia (TD) is a persistent and potentially disabling movement disorder associated with prolonged exposure to antipsychotics and other dopamine receptor blocking agents. Long-term safety of the approved TD medication, valbenazine, was demonstrated in 2 clinical trials (KINECT 3 [NCT02274558], KINECT 4 [NCT02405091]). Data from these trials were analyzed post hoc to evaluate the onset and resolution of adverse events (AEs).MethodsParticipants in KINECT 3 and KINECT 4 received up to 48 weeks of once-daily valbenazine (40 or 80 mg). Data from these studies were pooled and analyzed to assess the incidence, time to first occurrence, and resolution for the following AEs of potential clinical interest: akathisia, balance disorder, dizziness, parkinsonism, somnolence/sedation, suicidal behavior/ideation, and tremor.ResultsIn the pooled population (N=314), all AEs of potential clinical interest occurred in <10% of participants, with somnolence (9.6%), suicidal behavior/ideation (6.4%), and dizziness (5.7%) being the most common AEs. Mean time to first occurrence ranged from 36 days (akathisia [n=9]) to 224 days (parkinsonism [n=2]). By end of study (or last study visit), resolution of AEs was as follows: 100% (suicidal ideation/behavior, parkinsonism); >85% (somnolence/sedation, dizziness); >70% (akathisia, balance disorder, tremor).ConclusionsIn long-term clinical trials, the incidence of AEs of potential clinical interest was low (<10%) and most were resolved by end of treatment (>70–100%). All patients taking valbenazine should be routinely monitored for AEs, particularly those that may exacerbate the motor symptoms associated with TD.FundingNeurocrine Biosciences, Inc.

scholarly journals DNA Methylation Changes duringIn VitroPropagation of Human Mesenchymal Stem Cells: Implications for Their Genomic Stability?

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Angela Bentivegna ◽  
Mariarosaria Miloso ◽  
Gabriele Riva ◽  
Dana Foudah ◽  
Valentina Butta ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Ex Vivo ◽  
Genomic Stability ◽  
Great Promise ◽  
Human Mscs ◽  
Low Oxygen ◽  
Long Term Culture ◽  
Functional Changes

Mesenchymal stem cells (MSCs) hold great promise for the treatment of numerous diseases. A major problem for MSC therapeutic use is represented by the very low amount of MSCs which can be isolated from different tissues; thusex vivoexpansion is indispensable. Long-term culture, however, is associated with extensive morphological and functional changes of MSCs. In addition, the concern that they may accumulate stochastic mutations which lead the risk of malignant transformation still remains. Overall, the genome of human MSCs (hMSCs) appears to be apparently stable throughout culture, though transient clonal aneuploidies have been detected. Particular attention should be given to the use of low-oxygen environment in order to increase the proliferative capacity of hMSCs, since data on the effect of hypoxic culture conditions on genomic stability are few and contradictory. Furthermore, specific and reproducible epigenetic changes were acquired by hMSCs duringex vivoexpansion, which may be connected and trigger all the biological changes observed. In this review we address current issues on long-term culture of hMSCs with a 360-degree view, starting from the genomic profiles and back, looking for an epigenetic interpretation of their genetic stability.

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