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Cureus Sep 2022Drug overdose is a medico-social issue worldwide that may occur intentionally or unintentionally. It is one of the most common reasons for emergency department visits,...
BACKGROUND
Drug overdose is a medico-social issue worldwide that may occur intentionally or unintentionally. It is one of the most common reasons for emergency department visits, and it is also a frequent cause of morbidity and mortality globally. This study aims to determine the occurrence of acute toxicity cases and their management outcomes at the emergency departments in Qassim Province hospitals in Saudi Arabia. In addition, the study aims to investigate the antidote availabilities at those medical centers.
METHODS
A retrospective hospital record-based study of acute toxicity cases admitted to the emergency department in hospitals in Qassim during the period from January 1, 2020, to December 31, 2020, was conducted. Data were collected based on hospital resources such as gastrointestinal decontamination, stabilization, elimination enhancement resources, and antidotes from Qassim hospitals, and the availability of antidotes as well as the clinical data of the patients with the management outcome.
RESULTS
A total of 264 patients with acute toxicity were admitted to the emergency departments of 14 hospitals in Qassim Province in 2020. Of the 264 cases, 179 (68%) were males, and 85 (32%) cases were females. Ninety-five percent of the cases were admitted to public hospitals, whereas 5% were admitted to private hospitals. The largest group by age of admitted cases were aged 11-20 years (19.3%). This study showed that 99% received appropriate treatment for their cause of toxicity, whereas 1% did not. The most common causes of toxicity in Qassim were found to be food poisoning (20.5%), followed by intentional suicide attempts with warfarin/enoxaparin/aspirin overdoses (15.9%) and acetaminophen (paracetamol) overdosage seen in 15.5% of admitted cases. Flagyl, in addition to fluids, was used in the management of 16.7% of cases, N-acetyl cysteine was used for 16.3%, and vitamins K and B6 were used for 14.0% of cases. Activated charcoal, atropine, calcium chloride, calcium gluconate, flumazenil, insulin, magnesium, sodium bicarbonate, and vitamin K were available at all the studied hospitals. However, all the hospitals lacked both ethylenediaminetetraacetic acid (EDTA) and a cyanide kit. Methylene blue and leucovorin were available in only one of the studied hospitals.
PubMed: 36249602
DOI: 10.7759/cureus.28992 -
Journal of Materials Engineering and... 2023This work deals with the development of cyanide-free copper-silver electroplated coatings on AISI-1075 steel and its corrosion behavior under a 5% NaClO solution...
This work deals with the development of cyanide-free copper-silver electroplated coatings on AISI-1075 steel and its corrosion behavior under a 5% NaClO solution (commercial household bleach). A cyanide-free bath based on sodium thiosulfate was employed to obtain the silver coatings using current densities from 0.2 to 5.0 mA/cm and different concentrations of EDTA (additive). The evolution of the open circuit potential with time showed that silver is anodic with respect to copper, so there were no intense attacks in the silver pores. Adhesion measurements were made on both coatings by the tape test. The behavior against corrosion was evaluated by polarization resistance (Rp) in samples with the best coating adhesion. The best results were obtained with a silver coating of about 20 μm in thickness deposited on copper coating previously polished with colloidal silica. The best performance was attributed to the formation of AgCl as demonstrated by x-ray diffraction and scanning electron microscopy.
PubMed: 36068855
DOI: 10.1007/s11665-022-07270-w -
Journal, Genetic Engineering &... Aug 2022Endophytic bacteria overlay significant role in plant growth promotion, eliminating phyto-pathogens and combating stress-conditions. In the present study, we aimed to...
BACKGROUND
Endophytic bacteria overlay significant role in plant growth promotion, eliminating phyto-pathogens and combating stress-conditions. In the present study, we aimed to screen high salt tolerant bacteria and study their adaptive response to elevated salt concentrations. A total of 46 endophytic bacterial isolates from Vigna radiata were screened for salt tolerance. The high salt tolerant endophytic isolate was characterized for alteration in morphology, growth rate, protein profiling, and compatible solute concentrations.
RESULTS
The isolate MHN12, based upon biochemical characterization and partial 16S rDNA sequencing identified as B. licheniformis (accession number MG273753) was able to tolerate up to 15% NaCl (Sodium Chloride) (2.6 M) concentration. The isolate possessed 1-aminocyclopropane-1-carboxylic acid deaminase (ACCD) activity along with indole acetic acid (IAA), siderophore, ammonia, organic acid and hydrogen cyanide (HCN) production. Accumulation of proline was apparent up to 7.5% NaCl concentration and declined afterwards. Ultrastructure analysis using TEM (transmission electron microscopy) revealed the morphological alteration from rods to filaments.
CONCLUSION
Acclimatization to salt stress and plant growth promoting activities could contribute to utilization of this bacterium as bioinoculant to enhance the crop yield and discourage the application of chemical fertilizers.
PubMed: 35920988
DOI: 10.1186/s43141-022-00407-3 -
JHEP Reports : Innovation in Hepatology Aug 2022In cirrhosis, astrocytic swelling is believed to be the principal mechanism of ammonia neurotoxicity leading to hepatic encephalopathy (HE). The role of neuronal...
BACKGROUND & AIMS
In cirrhosis, astrocytic swelling is believed to be the principal mechanism of ammonia neurotoxicity leading to hepatic encephalopathy (HE). The role of neuronal dysfunction in HE is not clear. We aimed to explore the impact of hyperammonaemia on mitochondrial function in primary co-cultures of neurons and astrocytes and in acute brain slices of cirrhotic rats using live cell imaging.
METHODS
To primary cocultures of astrocytes and neurons, low concentrations (1 and 5 μM) of NHCl were applied. In rats with bile duct ligation (BDL)-induced cirrhosis, a model known to induce hyperammonaemia and minimal HE, acute brain slices were studied. One group of BDL rats was treated twice daily with the ammonia scavenger ornithine phenylacetate (OP; 0.3 g/kg). Fluorescence measurements of changes in mitochondrial membrane potential (Δψm), cytosolic and mitochondrial reactive oxygen species (ROS) production, lipid peroxidation (LP) rates, and cell viability were performed using confocal microscopy.
RESULTS
Neuronal cultures treated with NHCl exhibited mitochondrial dysfunction, ROS overproduction, and reduced cell viability (27.8 ± 2.3% and 41.5 ± 3.7%, respectively) compared with untreated cultures (15.7 ± 1.0%, both <0.0001). BDL led to increased cerebral LP ( = 0.0003) and cytosolic ROS generation ( <0.0001), which was restored by OP (both <0.0001). Mitochondrial function was severely compromised in BDL, resulting in hyperpolarisation of Δψm with consequent overconsumption of adenosine triphosphate and augmentation of mitochondrial ROS production. Administration of OP restored Δψm. In BDL animals, neuronal loss was observed in hippocampal areas, which was partially prevented by OP.
CONCLUSIONS
Our results elucidate that low-grade hyperammonaemia in cirrhosis can severely impact on brain mitochondrial function. Profound neuronal injury was observed in hyperammonaemic conditions, which was partially reversible by OP. This points towards a novel mechanism of HE development.
LAY SUMMARY
The impact of hyperammonaemia, a common finding in patients with liver cirrhosis, on brain mitochondrial function was investigated in this study. The results show that ammonia in concentrations commonly seen in patients induces severe mitochondrial dysfunction, overproduction of damaging oxygen molecules, and profound injury and death of neurons in rat brain cells. These findings point towards a novel mechanism of ammonia-induced brain injury in liver failure and potential novel therapeutic targets.
PubMed: 35845295
DOI: 10.1016/j.jhepr.2022.100510 -
Journal of Bacteriology Jul 2022Staphylococcus aureus Tet38 efflux pump has multiple functions, including conferring resistance to tetracycline and other compounds and enabling internalization and...
Staphylococcus aureus Tet38 efflux pump has multiple functions, including conferring resistance to tetracycline and other compounds and enabling internalization and survival within epithelial cells. In this study, we evaluated the effects of sodium and potassium on expression. These monovalent cations are known to play a role in transport by the related S. aureus TetK and B. subtilis TetL transporters. transcription decreased with increasing sodium concentrations by means of direct repression by the salt stress-dependent KdpD/E regulator. transcription increased 20-fold and tetracycline minimum inhibitory concentration (MIC) increased 4-fold in a Δ mutant. KdpE bound specifically to the promoter. Under extreme salt stress, the survival of S. aureus with intact was reduced compared to that of a Δ mutant. To study the effect of sodium on Tet38 function, we generated constructs overexpressing and and introduced them into Escherichia coli TO114, which is deficient in major sodium transporters. Tet38 tetracycline efflux was directly demonstrated in a fluorescence assay, and tetracycline efflux of both Tet38 and TetK was abolished by the protonophore carbonyl cyanide 3-chlorophenylhydrazone (CCCP). In contrast, NaCl inhibited efflux by Tet38 but not TetK, whereas KCl inhibited efflux by TetK but not Tet38. Cell-associated Na increased with heterologous overexpression of Tet38. These data indicate that S. aureus Tet38 is a tetracycline efflux pump regulated by the KdpD/E regulator. Under salt stress, S. aureus adjusted its survival in part by reducing the expression of through KdpD/E. The mechanisms by which Tet38 is detrimental to salt tolerance in S. aureus and inhibited by sodium remain to be determined. This study shows that S. aureus Tet38 is a tetracycline efflux pump regulated by KdpD/E regulator. These findings are the first direct demonstration of Tet38-mediated tetracycline efflux, which had previously been inferred from its ability to confer tetracycline resistance. Under salt stress, S. aureus adjusts its survival in part by reducing the expression of through KdpD/E. We demonstrated the differences in the respective functions of S. aureus Tet38 and other tetracycline efflux transporters (S. aureus TetK, B. subtilis TetL) regarding their transport of tetracycline and Na/K. Notably, sodium selectively reduced tetracycline efflux by Tet38, and potassium selectively reduced tetracycline efflux by TetK. The multiple functions of Tet38 emphasize its importance in bacterial adaptation to and survival in diverse environments.
Topics: Anti-Bacterial Agents; Bacterial Proteins; Escherichia coli; Escherichia coli Proteins; Membrane Transport Proteins; Microbial Sensitivity Tests; Potassium; Protein Kinases; Salt Stress; Sodium; Staphylococcus aureus; Tetracycline
PubMed: 35699453
DOI: 10.1128/jb.00142-22 -
International Journal of Molecular... May 2022Mitochondrial stress is involved in many pathological conditions and triggers the integrated stress response (ISR). The ISR is initiated by phosphorylation of the...
Mitochondrial stress is involved in many pathological conditions and triggers the integrated stress response (ISR). The ISR is initiated by phosphorylation of the eukaryotic translation initiation factor (eIF) 2α and results in global inhibition of protein synthesis, while the production of specific proteins important for the stress response and recovery is favored. The stalled translation preinitiation complexes phase-separate together with local RNA binding proteins into cytoplasmic stress granules (SG), which are important for regulation of cell signaling and survival under stress conditions. Here we found that mitochondrial inhibition by sodium azide (NaN) in mammalian cells leads to translational inhibition and formation of SGs, as previously shown in yeast. Although mammalian NaN-induced SGs are very small, they still contain the canonical SG proteins Caprin 1, eIF4A, eIF4E, eIF4G and eIF3B. Similar to FCCP and oligomycine, other mitochodrial stressors that cause SG formation, NaN-induced SGs are formed by an eIF2α phosphorylation-independent mechanisms. Finally, we discovered that as shown for arsenite (ASN), but unlike FCCP or heatshock stress, Thioredoxin 1 (Trx1) is required for formation of NaN-induced SGs.
Topics: Animals; Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; Cytoplasmic Granules; Eukaryotic Initiation Factor-2; Mammals; Phosphorylation; RNA-Binding Proteins; Saccharomyces cerevisiae; Sodium Azide; Stress Granules
PubMed: 35628412
DOI: 10.3390/ijms23105600 -
Medicina (Kaunas, Lithuania) Apr 2022: The commissural nucleus of the tractus solitarius (cNTS) not only responds to glucose levels directly, but also receives afferent signals from the liver, and from the...
Leptin in the Commissural Nucleus of the Tractus Solitarius (cNTS) and Anoxic Stimulus in the Carotid Body Chemoreceptors Increases cNTS Leptin Signaling Receptor and Brain Glucose Retention in Rats.
: The commissural nucleus of the tractus solitarius (cNTS) not only responds to glucose levels directly, but also receives afferent signals from the liver, and from the carotid chemoreceptors (CChR). In addition, leptin, through its receptors in the cNTS, regulates food intake, body weight, blood glucose levels, and brain glucose retention (BGR). These leptin effects on cNTS are thought to be mediated through the sympathetic-adrenal system. How these different sources of information converging in the NTS regulate blood glucose levels and brain glucose retention remains largely unknown. The goal of the present study was to determine whether the local administration of leptin in cNTS alone, or after local anoxic stimulation using sodium cyanide (NaCN) in the carotid sinus, modifies the expression of leptin and of mRNA. We also investigated how leptin, alone, or in combination with carotid sinus stimulation, affected brain glucose retention. : The experiments were carried out in anesthetized male Wistar rats artificially ventilated to maintain homeostatic values for pO, pCO, and pH. We had four groups: (a) experimental 1, leptin infusion in cNTS and NaCN in the isolated carotid sinus (ICS; = 10); (b) experimental 2, leptin infusion in cNTS and saline in the ICS ( = 10); (c) control 1, artificial cerebrospinal fluid (aCSF) in cNTS and NaCN in the ICS ( = 10); (d) control 2, aCSF in cNTS and saline in the ICS ( = 10). : Leptin in cNTS, preceded by NaCN in the ICS increased BGR and leptin mRNA receptor expression, with no significant increases in mRNA in the NTSc. : Leptin in the cNTS enhances brain glucose retention induced by an anoxic stimulus in the carotid chemoreceptors, through an increase in receptors, without persistent changes in neuronal activation.
Topics: Animals; Blood Glucose; Carotid Body; Glucose; Hypoxia; Leptin; Male; RNA, Messenger; Rats; Rats, Wistar; Receptors, Leptin; Solitary Nucleus
PubMed: 35454388
DOI: 10.3390/medicina58040550 -
Oxidative Medicine and Cellular... 2022Intervertebral disc (IVD) degeneration (IDD), the leading cause of low back pain (LBP), remains intractable due to a lack of effective therapeutic strategies. Several...
Intervertebral disc (IVD) degeneration (IDD), the leading cause of low back pain (LBP), remains intractable due to a lack of effective therapeutic strategies. Several lines of studies have documented that nucleus pulposus cell (NPC) death induced by excessive oxidative stress is a crucial contributor to IDD. However, the concrete role and regulation mechanisms have not been fully clarified. Selenium (Se), a vital prosthetic group of antioxidant enzymes, is indispensable for maintaining redox homeostasis and promoting cell survival. However, no light was shed on the role of Se on IDD progression, especially regulation on mitochondrial dynamics and homeostasis. To fill this research gap, the current study focuses on the effects of Se, including sodium selenite (SS) and selenomethionine (Se-Met), on IDD progression and the underlying mechanisms. In vitro, we found that both SS and Se-Met alleviated tert-butyl hydroperoxide- (TBHP-) induced oxidative stress, protected mitochondrial function, and inhibited apoptosis of NPCs. Further experiments indicated that Se suppressed TBHP-induced mitochondrial fission and rescued the imbalance of mitochondrial dynamics. Promoting mitochondrial fission by carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (FCCP) partially counteracted the cytoprotective effects of Se. Moreover, blocking nuclear factor erythroid 2-related factor 2 (Nrf2) with ML385 proved that the effect of Se on regulating mitochondrial dynamics was attributed to the activation of the Nrf2 pathway. In the puncture-induced rat IDD model, a supplement of Se-Met ameliorated degenerative manifestations. Taken together, our results demonstrated that Se suppressed TBHP-induced oxidative stress and mitochondrial fission by activating the Nrf2 pathway, thereby inhibiting the apoptosis of NPCs and ameliorating IDD. Regulation of mitochondrial dynamics by Se may have a potential application value in attenuating the pathological process of IDD.
Topics: Animals; Antioxidants; Apoptosis; Intervertebral Disc Degeneration; Mitochondrial Dynamics; NF-E2-Related Factor 2; Nucleus Pulposus; Rats; Selenium
PubMed: 35450408
DOI: 10.1155/2022/7531788 -
Biomedical Journal Feb 2022The central clock of the suprachiasmatic nucleus (SCN) controls the metabolism of glucose and is sensitive to glucose shortage. However, it is only beginning to be...
Glycolytic metabolism and activation of Na pumping contribute to extracellular acidification in the central clock of the suprachiasmatic nucleus: Differential glucose sensitivity and utilization between oxidative and non-oxidative glycolytic pathways.
BACKGROUND
The central clock of the suprachiasmatic nucleus (SCN) controls the metabolism of glucose and is sensitive to glucose shortage. However, it is only beginning to be understood how metabolic signals such as glucose availability regulate the SCN physiology. We previously showed that the ATP-sensitive K channel plays a glucose-sensing role in regulating SCN neuronal firing at times of glucose shortage. Nevertheless, it is unknown whether the energy-demanding Na/K-ATPase (NKA) is also sensitive to glucose availability. Furthermore, we recently showed that the metabolically active SCN constantly extrudes H to acidify extracellular pH (pHe). This study investigated whether the standing acidification is associated with Na pumping activity, energy metabolism, and glucose utilization, and whether glycolysis- and mitochondria-fueled NKAs may be differentially sensitive to glucose shortage.
METHODS
Double-barreled pH-selective microelectrodes were used to determine the pHe in the SCN in hypothalamic slices.
RESULTS
NKA inhibition with K-free (0-K) solution rapidly and reversibly alkalinized the pHe, an effect abolished by ouabain. Mitochondrial inhibition with cyanide acidified the pHe but did not inhibit 0-K-induced alkalinization. Glycolytic inhibition with iodoacetate alkalinized the pHe, completely blocked cyanide-induced acidification, and nearly completely blocked 0-K-induced alkalinization. The results indicate that glycolytic metabolism and activation of Na pumping contribute to the standing acidification. Glucoprivation also alkalinized the pHe, nearly completely eliminated cyanide-induced acidification, but only partially reduced 0-K-induced alkalinization. In contrast, hypoglycemia preferentially and partially blocked cyanide-induced acidification. The result indicates sensitivity to glucose shortage for the mitochondria-associated oxidative glycolytic pathway.
CONCLUSION
Glycolytic metabolism and activation of glycolysis-fueled NKA Na pumping activity contribute to the standing acidification in the SCN. Furthermore, the oxidative and non-oxidative glycolytic pathways differ in their glucose sensitivity and utilization, with the oxidative glycolytic pathway susceptible to glucose shortage, and the non-oxidative glycolytic pathway able to maintain Na pumping even in glucoprivation.
Topics: Cyanides; Glucose; Glycolysis; Humans; Hydrogen-Ion Concentration; Oxidative Stress; Sodium; Suprachiasmatic Nucleus
PubMed: 35341719
DOI: 10.1016/j.bj.2021.02.004 -
Current Neuropharmacology 2023Neuronal injury during acute hypoxia, ischemia, and following reperfusion are partially attributable to oxidative damage caused by deleterious fluctuations of reactive...
Neuronal injury during acute hypoxia, ischemia, and following reperfusion are partially attributable to oxidative damage caused by deleterious fluctuations of reactive oxygen species (ROS). In particular, mitochondrial superoxide (O•-) production is believed to upsurge during lowoxygen conditions and also following reperfusion, before being dismutated to HO and released into the cell. However, disruptions of redox homeostasis may be beneficially attenuated in the brain of hypoxia-tolerant species, such as the naked mole-rat (NMR, Heterocephalus glaber). As such, we hypothesized that ROS homeostasis is better maintained in the brain of NMRs during severe hypoxic/ ischemic insults and following reperfusion. We predicted that NMR brain would not exhibit substantial fluctuations in ROS during hypoxia or reoxygenation, unlike previous reports from hypoxiaintolerant mouse brain. To test this hypothesis, we measured cortical ROS flux using corrected total cell fluorescence measurements from live brain slices loaded with the MitoSOX red superoxide (O•-) indicator or chloromethyl 2',7'-dichlorodihydrofluorescein diacetate (CM-H-DCFDA; which fluoresces with whole-cell hydrogen peroxide (HO) production) during various low-oxygen treatments, exogenous oxidative stress, and reperfusion. We found that NMR cortex maintained ROS homeostasis during low-oxygen conditions, while mouse cortex exhibited a ~40% increase and a ~30% decrease in mitochondrial O•- and cellular HO production, respectively. Mitochondrial ROS homeostasis in NMRs was only disrupted following sodium cyanide application, which was similarly observed in mice. Our results suggest that NMRs have evolved strategies to maintain ROS homeostasis during acute bouts of hypoxia and reoxygenation, potentially as an adaptation to life in an intermittently hypoxic environment.
Topics: Animals; Mice; Reactive Oxygen Species; Superoxides; Hydrogen Peroxide; Hypoxia; Oxygen; Ischemia; Reperfusion; Mole Rats
PubMed: 35339183
DOI: 10.2174/1570159X20666220327220929