-
Cureus Apr 2024The diagnosis of death from potassium chloride (KCl) injection is complex because it is a natural ion, so it is very difficult to trace the exogenous administration of...
The diagnosis of death from potassium chloride (KCl) injection is complex because it is a natural ion, so it is very difficult to trace the exogenous administration of drugs containing potassium. In these cases, it is important to perform a careful cadaver inspection, with the collection of circumstantial data on the scene, and proper autopsy investigations, in order to avoid errors regarding the reconstruction of the cause of death. The aim of this paper is to propose a forensic protocol, including evidence collected from the literature, that could help the medical examiner to perform the correct diagnosis, and also encourage control measures to avoid similar events, especially in nosocomial environments. This is important, especially for health professionals who can easily access drugs containing potassium. For this reason, we need to strengthen control measures of these drugs by proposing a double check in cases of pharmacological use, specifying the volume taken with a double authorization signature and the reasons for the withdrawal.
PubMed: 38716018
DOI: 10.7759/cureus.57776 -
Biology Open May 2024Recent research has shown that membrane trafficking plays an important role in canonical Wnt signaling through sequestration of the β-catenin destruction complex inside...
Recent research has shown that membrane trafficking plays an important role in canonical Wnt signaling through sequestration of the β-catenin destruction complex inside multivesicular bodies (MVBs) and lysosomes. In this study, we introduce Ouabain, an inhibitor of the Na,K-ATPase pump that establishes electric potentials across membranes, as a potent inhibitor of Wnt signaling. We find that Na,K-ATPase levels are elevated in advanced colon carcinoma, that this enzyme is elevated in cancer cells with constitutively activated Wnt pathway and is activated by GSK3 inhibitors that increase macropinocytosis. Ouabain blocks macropinocytosis, which is an essential step in Wnt signaling, probably explaining the strong effects of Ouabain on this pathway. In Xenopus embryos, brief Ouabain treatment at the 32-cell stage, critical for the earliest Wnt signal in development-inhibited brains, could be reversed by treatment with Lithium chloride, a Wnt mimic. Inhibiting membrane trafficking may provide a way of targeting Wnt-driven cancers.
Topics: Wnt Signaling Pathway; Pinocytosis; Colonic Neoplasms; Sodium-Potassium-Exchanging ATPase; Animals; Humans; Ouabain; Cell Line, Tumor; Xenopus
PubMed: 38713004
DOI: 10.1242/bio.060269 -
Current Oral Health Reports 2024Dental caries or tooth decay is one of the communal problems in the world which can affect not only the oral health but also the general health conditions. The main... (Review)
Review
PURPOSE OF REVIEW
Dental caries or tooth decay is one of the communal problems in the world which can affect not only the oral health but also the general health conditions. The main objective of this systematic review is to explore the efficacy of bioactive glass-based toothpastes against cariogenic bacteria.
RECENT FINDINGS
Bioactive glass particulates containing toothpaste show better remineralization potential on demineralized enamel and dentin when compared with toothpaste containing various bioactive constituents such as fluoride and potassium chloride. These constituents in conventional toothpaste can rapidly streak off due to acidic impact in the oral environment as the bioactive glass provides minerals for demineralized enamel and dentin by forming a strong hydroxyapatite (HAp) layer on its surface. Further, the therapeutic ions present in the bioglass can resist plaque formation by raising the pH of the surrounding environment or saliva and create amicable media for healthier teeth.
SUMMARY
Toothpaste containing bioactive glass particles undoubtedly displayed the remineralizing potentiality of the dental hard tissues. Dynamics of the mineralization through different bioactive glass materials needs further investigations. In order to prevent dental cavities and improve oral health, it is important to identify and study different effective bioglass particles in toothpaste.
PubMed: 38706577
DOI: 10.1007/s40496-024-00366-3 -
BMC Pediatrics May 2024Congenital chloride diarrhoea (CCD) is an autosomal recessive condition that causes secretory diarrhoea and potentially deadly electrolyte imbalances in infants because...
INTRODUCTION
Congenital chloride diarrhoea (CCD) is an autosomal recessive condition that causes secretory diarrhoea and potentially deadly electrolyte imbalances in infants because of solute carrier family 26 member 3 (SLC26A3) gene mutations.
CASE PRESENTATION
A 7-month-old Chinese infant with a history of maternal polyhydramnios presented with frequent watery diarrhoea, severe dehydration, hypokalaemia, hyponatraemia, failure to thrive, metabolic alkalosis, hyperreninaemia, and hyperaldosteronaemia. Genetic testing revealed a compound heterozygous SLC26A3 gene mutation in this patient (c.269_270dup and c.2006 C > A). Therapy was administered in the form of oral sodium and potassium chloride supplements, which decreased stool frequency.
CONCLUSIONS
CCD should be considered when an infant presents with prolonged diarrhoea during infancy, particularly in the context of maternal polyhydramnios and dilated foetal bowel loops.
Topics: Female; Humans; Infant; Male; Chloride-Bicarbonate Antiporters; Diarrhea; East Asian People; Heterozygote; Metabolism, Inborn Errors; Mutation; Polyhydramnios; Potassium Chloride; Sulfate Transporters
PubMed: 38704545
DOI: 10.1186/s12887-024-04788-x -
High serum sodium predicts immunotherapy response in metastatic renal cell and urothelial carcinoma.European Journal of Cancer (Oxford,... Jun 2024The development of reliable biomarkers for the prediction of immune checkpoint inhibition (ICI) response in patients with metastatic renal cell carcinoma (mRCC) and...
OBJECTIVES
The development of reliable biomarkers for the prediction of immune checkpoint inhibition (ICI) response in patients with metastatic renal cell carcinoma (mRCC) and urothelial carcinoma (mUC) remains an unresolved challenge. Conventional ICI biomarkers typically focus on tumor-related factors such as PD-L1 expression. However, a comprehensive evaluation of the predictive value of serum electrolyte levels, a so far widely unexplored area, is still pending.
METHODS
We conducted a post-hoc analysis of baseline sodium, potassium, chloride, magnesium and calcium levels in two independent phase 3 clinical trials: IMvigor211 for mUC comparing atezolizumab to chemotherapy, and IMmotion151 for mRCC comparing atezolizumab+bevacizumab to sunitinib. This analysis aimed to evaluate the prognostic and predictive value of these electrolyte levels in these clinical settings. A total of 1787 patients (IMvigor211 n = 901; IMmotion151 n = 886) were analyzed.
RESULTS
We found a linear correlation of baseline serum sodium and chloride with prognosis across both trials, which was not found for potassium, magnesium and calcium. In multivariate analysis, the prognostic capacity of sodium was limited to patients receiving ICI as compared to the control group. Interestingly, in both studies, the chance of achieving an objective response was highest in the patient subgroup with high baseline serum sodium levels of > 140 mmol/L (IMmotion151: Complete response in 17.9% versus 2.0% in patients with mRCC with baseline sodium < 135 mmol/L). Serum sodium outperformed tumor PD-L1 expression as a predictor for immunotherapy efficacy.
CONCLUSIONS
Patients exhibiting elevated serum sodium levels derive the greatest benefit from immunotherapy, suggesting that baseline serum concentration could serve as a valuable and cost-effective predictive biomarker for immunotherapy across entities.
Topics: Humans; Kidney Neoplasms; Male; Carcinoma, Renal Cell; Female; Sodium; Aged; Middle Aged; Immunotherapy; Antibodies, Monoclonal, Humanized; Bevacizumab; Biomarkers, Tumor; Immune Checkpoint Inhibitors; Prognosis; Antineoplastic Combined Chemotherapy Protocols; Sunitinib; Carcinoma, Transitional Cell
PubMed: 38703618
DOI: 10.1016/j.ejca.2024.114089 -
Scientific Reports May 2024Spreading depolarizations (SDs) occur frequently in patients with malignant hemispheric stroke. In animal-based experiments, SDs have been shown to cause secondary...
Spreading depolarizations (SDs) occur frequently in patients with malignant hemispheric stroke. In animal-based experiments, SDs have been shown to cause secondary neuronal damage and infarct expansion during the initial period of infarct progression. In contrast, the influence of SDs during the delayed period is not well characterized yet. Here, we analyzed the impact of SDs in the delayed phase after cerebral ischemia and the potential protective effect of ketamine. Focal ischemia was induced by distal occlusion of the left middle cerebral artery in C57BL6/J mice. 24 h after occlusion, SDs were measured using electrocorticography and laser-speckle imaging in three different study groups: control group without SD induction, SD induction with potassium chloride, and SD induction with potassium chloride and ketamine administration. Infarct progression was evaluated by sequential MRI scans. 24 h after occlusion, we observed spontaneous SDs with a rate of 0.33 SDs/hour which increased during potassium chloride application (3.37 SDs/hour). The analysis of the neurovascular coupling revealed prolonged hypoemic and hyperemic responses in this group. Stroke volume increased even 24 h after stroke onset in the SD-group. Ketamine treatment caused a lesser pronounced hypoemic response and prevented infarct growth in the delayed phase after experimental ischemia. Induction of SDs with potassium chloride was significantly associated with stroke progression even 24 h after stroke onset. Therefore, SD might be a significant contributor to delayed stroke progression. Ketamine might be a possible drug to prevent SD-induced delayed stroke progression.
Topics: Ketamine; Animals; Mice; Male; Mice, Inbred C57BL; Brain Ischemia; Disease Progression; Disease Models, Animal; Magnetic Resonance Imaging; Cortical Spreading Depression; Infarction, Middle Cerebral Artery
PubMed: 38702377
DOI: 10.1038/s41598-024-59835-5 -
Journal of Cellular and Molecular... May 2024Gliomas, the most lethal tumours in brain, have a poor prognosis despite accepting standard treatment. Limited benefits from current therapies can be attributed to...
Gliomas, the most lethal tumours in brain, have a poor prognosis despite accepting standard treatment. Limited benefits from current therapies can be attributed to genetic, epigenetic and microenvironmental cues that affect cell programming and drive tumour heterogeneity. Through the analysis of Hi-C data, we identified a potassium-chloride co-transporter SLC12A5 associated with disrupted topologically associating domain which was downregulated in tumour tissues. Multiple independent glioma cohorts were included to analyse the characterization of SLC12A5 and found it was significantly associated with pathological features, prognostic value, genomic alterations, transcriptional landscape and drug response. We constructed two SLC12A5 overexpression cell lines to verify the function of SLC12A5 that suppressed tumour cell proliferation and migration in vitro. In addition, SLC12A5 was also positively associated with GABA receptor activity and negatively associated with pro-tumour immune signatures and immunotherapy response. Collectively, our study provides a comprehensive characterization of SLC12A5 in glioma and supports SLC12A5 as a potential suppressor of disease progression.
Topics: Humans; Glioma; Gene Expression Regulation, Neoplastic; Cell Proliferation; Cell Line, Tumor; Brain Neoplasms; Symporters; Cell Movement; Prognosis; Receptors, GABA-A; K Cl- Cotransporters
PubMed: 38685685
DOI: 10.1111/jcmm.18352 -
Micromachines Apr 2024A surface acoustic wave (SAW) resonator chip setup is presented that eliminates interfering signal responses caused by changes in the electrical environment of the...
A surface acoustic wave (SAW) resonator chip setup is presented that eliminates interfering signal responses caused by changes in the electrical environment of the surrounding media. When using a two-port resonator, applying electrically shielding layers between the interdigital transducers (IDTs) can be challenging due to the limited dimensions. Therefore, a layered setup consisting of an insulating polymer layer and a conductive gold layer was preferred. The SAW resonators were provided with polycarbonate housings, resulting in SAW resonator chips. This setup enables easy application of a wide range of coatings to the active part of the resonator surface, while ensuring subsequent electrical and fluidic integration of the resonator chips into a microfluidic array for measurements. The signal responses of uncoated SAW resonators and those with polymer coatings with and without a gold layer were tested with aqueous potassium chloride (KCl) solutions up to 3 mol/L, corresponding to conductivities up to 308 mS/cm. The use of a polymer coating at the thickness of the first Love mode resonance and a conductive gold layer completely reduced the electrical impact on the SAW resonator signal response, making small signals resulting from changes in viscosity and density of the KCl solutions visible.
PubMed: 38675312
DOI: 10.3390/mi15040501 -
International Journal of Molecular... Apr 2024Slc4a genes encode various types of transporters, including Na-HCO cotransporters, Cl/HCO exchangers, or Na-driven Cl/HCO exchangers. Previous research has revealed that...
Slc4a genes encode various types of transporters, including Na-HCO cotransporters, Cl/HCO exchangers, or Na-driven Cl/HCO exchangers. Previous research has revealed that Slc4a9 (Ae4) functions as a Cl/HCO exchanger, which can be driven by either Na or K, prompting investigation into whether other Slc4a members facilitate cation-dependent anion transport. In the present study, we show that either Na or K drive Cl/HCO exchanger activity in cells overexpressing Slc4a8 or Slc4a10. Further characterization of cation-driven Cl/HCO exchange demonstrated that Slc4a8 and Slc4a10 also mediate Cl and HCO-dependent K transport. Full-atom molecular dynamics simulation on the recently solved structure of Slc4a8 supports the coordination of K at the Na binding site in S1. Sequence analysis shows that the critical residues coordinating monovalent cations are conserved among mouse Slc4a8 and Slc4a10 proteins. Together, our results suggest that Slc4a8 and Slc4a10 might transport K in the same direction as HCO ions in a similar fashion to that described for Na transport in the rat Slc4a8 structure.
Topics: Animals; Mice; Bicarbonates; Binding Sites; Chloride-Bicarbonate Antiporters; Chlorides; Ion Transport; Molecular Dynamics Simulation; Potassium; Sodium; Sodium-Bicarbonate Symporters
PubMed: 38674160
DOI: 10.3390/ijms25084575 -
Materials (Basel, Switzerland) Apr 2024In seasonally frozen regions, concrete pavement is exposed to cycles of freeze-thaw and erosion from de-icing salt, which can lead to unfavorable service conditions and...
In seasonally frozen regions, concrete pavement is exposed to cycles of freeze-thaw and erosion from de-icing salt, which can lead to unfavorable service conditions and vulnerability to damage. This paper examines the compressive strength, flexural-tensile strength, abrasion resistance, permeability, and spacing factor of concrete, taking into account the impact of various curing conditions, de-icing salt solutions, and mass fractions on the concrete's freeze-thaw resistance. Two test methods, the single-face method and the fast-freezing method, were used to comparatively analyze the freeze-thaw resistance of concrete. The analysis was based on the surface scaling, water absorption rate, mass loss rate, relative dynamic elastic modulus, and relative durability index. The results indicate that the presence of salt solution significantly worsened the degree of concrete damage caused by freeze-thaw cycles. The use of freeze-thaw media, specifically sodium chloride (NaCl), calcium chloride (CaCl2), and potassium acetate (KAc) at mass fractions of 5%, 4.74%, and 5%, respectively, had the greatest impact on the surface scaling of concrete. However, their effect on the water absorption rate was inconsistent. When the freeze-thaw medium was water, the concrete's relative dynamic elastic modulus and relative durability index were 9.6% and 75.3% higher, respectively, for concrete cured in 20 °C-95% RH conditions compared to those cured in 0 °C-50% RH conditions. We propose a comprehensive relative durability index (DFw) by combining the results of two methods of freeze-thaw tests. The DFw of concrete cured in 0 °C-50% RH conditions was 83.8% lower than that of concrete cured in 20 °C-95% RH conditions when exposed to a freeze-thaw medium of 5% mass fraction NaCl solution. To evaluate the salt freeze-thaw resistance of concrete pavement, it is recommended to use surface scaling and DFw together.
PubMed: 38673259
DOI: 10.3390/ma17081902