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ACS Omega Apr 2024Chromium(III) complexes bearing bidentate {NH(CH)PPh: PN, ()-[NH(CHPh)PPh]: P'N} and tridentate [PhP(CH)N(H)(CH)PPh: P-NH-P, ()-(Pr)PCHCHN(H)CH(Ph)CH(Ph)PPh: P-NH-P']...
Chromium(III) complexes bearing bidentate {NH(CH)PPh: PN, ()-[NH(CHPh)PPh]: P'N} and tridentate [PhP(CH)N(H)(CH)PPh: P-NH-P, ()-(Pr)PCHCHN(H)CH(Ph)CH(Ph)PPh: P-NH-P'] ligands have been synthesized using a mechanochemical approach. The complexes {-[Cr(PN)Cl]Cl (), -[Cr(P'N)Cl]Cl (), -Cr(P-NH-P)Cl (), and -Cr(P-NH-P')Cl ()} were obtained in high yield (95-97%) the grinding of the respective ligands andthe solid Cr(III) ion precursor [CrCl(THF)] with the aid of a pestle and mortar, followed by recrystallization in acetonitrile. The isolated complexes are high spin. A single-crystal X-ray diffraction study of revealed a cationic chromium complex with two P'N ligands in a configuration with P' to P' with chloride as the counteranion. The X-ray study of shows a neutral Cr(III) complex with the P-NH-P' ligand in a configuration. The difference in molecular structures and bulkiness of the ligands influence the electronic, magnetic, and electrochemical properties of the complexes as exhibited by the bathochromic shifts in the electronic absorption peaks of the complexes and the relative increase in the magnetic moment of (4.19 μ) and (4.15 μ) above the spin only value (3.88 μ) for a d electronic configuration. Complexes - were found to be inactive in the hydrogenation of an aldimine [()-1-(4-fluorophenyl)--phenylmethanimine] under a variety of activating conditions. The addition of magnesium and trimethylsilyl chloride in THF did cause hydrogenation at room temperature, but this occurred even in the absence of the chromium complex. The hydrogen in the amine product came from the THF solvent in this novel reaction, as determined by deuterium incorporation into the product when deuterated THF was used.
PubMed: 38708235
DOI: 10.1021/acsomega.4c02076 -
The Science of the Total Environment Jun 2024Anthropogenic activities such as the over-application of road deicers are causing an increase in the concentration of salts in historically fresh waters. Experimental...
Anthropogenic activities such as the over-application of road deicers are causing an increase in the concentration of salts in historically fresh waters. Experimental and field investigations demonstrate that freshwater salinization disrupts ecosystem functions and services, causing the death of freshwater organisms and changes to nutrient conditions. Wetland habitats are one system negatively affected by salt pollution, including ephemeral wetlands (vernal pools) that fill with salt-polluted water after snowmelt. In urbanized areas, the degradation of these ecosystems could result in irreversible ecological damage including reduced water quality and a reduction in biodiversity. To investigate the effects of freshwater salinization on vernal pool communities, we exposed soils from vernal pools to water containing no salt (control), or four concentrations of three salts standardized by chloride concentration (50 mg Cl L, 100 mg Cl L, 200 mg Cl L, and 400 mg Cl L; magnesium chloride, calcium chloride, and sodium chloride). The results of this experiment suggest that emerging zooplankton communities in vernal pools are sensitive to low concentrations of salt pollution, and that alternative salts such as magnesium chloride and calcium chloride are more toxic than sodium chloride. We did not find positive or negative changes in the abundance of eukaryotic phytoplankton but did find negative effects of salt on cyanobacteria abundance, possibly due to corresponding reductions in turbidity which might be needed as a fixation site for cyanobacteria to form heterocysts. Finally, we found that salt pollution likely caused flocculation of Dissolved Organic Matter (DOM), resulting in reduced concentrations of DOM which could alter the buffering capacity of freshwater systems, light attenuation, and the populations of planktonic heterotrophs.
Topics: Cyanobacteria; Wetlands; Water Pollutants, Chemical; Fresh Water; Environmental Monitoring; Sodium Chloride; Salinity; Phytoplankton
PubMed: 38703853
DOI: 10.1016/j.scitotenv.2024.172948 -
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 -
EJNMMI Radiopharmacy and Chemistry Apr 20246-Bromo-7-[C]methylpurine ([C]BMP) is a radiotracer for positron emission tomography (PET) to measure multidrug resistance-associated protein 1 (MRP1) transport activity...
BACKGROUND
6-Bromo-7-[C]methylpurine ([C]BMP) is a radiotracer for positron emission tomography (PET) to measure multidrug resistance-associated protein 1 (MRP1) transport activity in different tissues. Previously reported radiosyntheses of [C]BMP afforded a mixture of 7- and 9-[C]methyl regioisomers. To prepare for clinical use, we here report an improved regioselective radiosynthesis of [C]BMP, the results of a non-clinical toxicity study as well as human dosimetry estimates based on mouse PET data.
RESULTS
[C]BMP was synthesised by regioselective N-methylation of 6-bromo-7H-purine (prepared under good manufacturing practice) with [C]methyl triflate in presence of 2,2,6,6-tetramethylpiperidine magnesium chloride in a TRACERlab™ FX2 C synthesis module. [C]BMP was obtained within a total synthesis time of approximately 43 min in a decay-corrected radiochemical yield of 20.5 ± 5.2%, based on starting [C]methyl iodide, with a radiochemical purity > 99% and a molar activity at end of synthesis of 197 ± 130 GBq/μmol (n = 28). An extended single-dose toxicity study conducted in male and female Wistar rats under good laboratory practice after single intravenous (i.v.) administration of unlabelled BMP (2 mg/kg body weight) revealed no test item related adverse effects. Human dosimetry estimates, based on dynamic whole-body PET data in female C57BL/6J mice, suggested that an i.v. injected activity amount of 400 MBq of [C]BMP will deliver an effective dose in the typical range of C-labelled radiotracers.
CONCLUSIONS
[C]BMP can be produced in sufficient amounts and acceptable quality for clinical use. Data from the non-clinical safety evaluation showed no adverse effects and suggested that the administration of [C]BMP will be safe and well tolerated in humans.
PubMed: 38683266
DOI: 10.1186/s41181-024-00265-z -
Medicina (Kaunas, Lithuania) Apr 2024: The purpose of this study was to investigate the influence induced by magnesium chloride (MgCl) and zinc gluconate (ZnG) supplementation on liver and kidney injuries...
: The purpose of this study was to investigate the influence induced by magnesium chloride (MgCl) and zinc gluconate (ZnG) supplementation on liver and kidney injuries experimentally induced with acetaminophen (AAPh) and potentiated by a ciprofloxacin addition in rats. : The experiment was performed on five animal groups: group 1-control, treated for 6 weeks with normal saline, 1 mL/kg; group 2-AAPh, treated for 6 weeks with AAPh, 100 mg/kg/day; group 3-AAPh + C, treated for 6 weeks with AAPh 100 mg/kg/day and ciprofloxacin 50 mg/kg/day, only in the last 14 days of the experiment; group 4-AAPh + C + Mg, with the same treatment as group 3, but in the last 14 days, MgCl 10 mg/ kg/day was added; and group 5-AAPh + C + Zn, with the same treatment as group 3, but in the last 14 days, zinc gluconate (ZnG), 10 mg/kg/day was added. All administrations were performed by oral gavage. At the end of the experiment, the animals were sacrificed and blood samples were collected for biochemistry examinations. : Treatment with AAPh for 6 weeks determined an alteration of the liver function (increases in alanine aminotransferase, aspartate aminotransferase, lactic dehydrogenase, and gamma-glutamyl transferase) and of renal function (increases in serum urea and creatinine) ( < 0.001 group 2 vs. group 1 for all mentioned parameters). Furthermore, the antioxidant defense capacity was impaired in group 2 vs. group 1 (superoxide dismutase and glutathione peroxidase activity decreased in group 2 vs. group 1, at 0.001 < < 0.01 and 0.01 < < 0.05, respectively). The addition of ciprofloxacin, 50 mg/kg/day during the last 14 days, resulted in further increases in alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, urea, and creatinine (0.01 < < 0.05, group 3 vs. group 2). MgCl provided a slight protection against the increase in liver enzymes, and a more pronounced protection against the increase in serum urea and creatinine (0.001 < < 0.01 group 4 vs. group 3). MgCl provided a slight protection against the decrease in superoxide dismutase (0.01 < < 0.05 group 4 vs. group 3), but not against decrease of glutathione peroxidase. The improvement of mentioned parameters could also be seen in the case of ZnG, to a higher extent, especially in the case of alanine aminotransferase and lactic dehydrogenase (0.01 < < 0.05 group 5 vs. group 4). : This study presents further proof for the beneficial effect of magnesium and zinc salts against toxicity induced by different agents, including antibacterials added to the analgesic and antipyretic acetaminophen; the protection is proven on the liver and kidney's function, and the antioxidant profile improvement has a key role, especially in the case of zinc gluconate.
Topics: Animals; Ciprofloxacin; Rats; Acetaminophen; Gluconates; Male; Rats, Wistar; Zinc; Kidney; Magnesium; Liver; Chemical and Drug Induced Liver Injury; Magnesium Chloride; Alanine Transaminase; Aspartate Aminotransferases; Drug Synergism
PubMed: 38674257
DOI: 10.3390/medicina60040611 -
Nanomaterials (Basel, Switzerland) Apr 2024A composite material composed of anodized aluminum oxide (AAO), carbon (C), and magnesium oxide (MgO) was developed for CO capture applications. Inspired by the...
A composite material composed of anodized aluminum oxide (AAO), carbon (C), and magnesium oxide (MgO) was developed for CO capture applications. Inspired by the bryophyte organism, the AAO/C/MgO composite mirrors two primary features of these species-(1) morphological characteristics and (2) elemental composition-specifically carbon, oxygen, and magnesium. The synthesis process involved two sequential steps: electroanodization of aluminum foil followed by a hydrothermal method using a mixture of glucose and magnesium chloride (MgCl). The concentration of MgCl was systematically varied as the sole experimental variable across five levels-1 mM, 2 mM, 3 mM, 4 mM, and 5 mM-to investigate the impact of MgO formation on the samples' chemical and physical properties, and consequently, their CO capture efficiency. Thus, scanning electron microscopy analysis revealed the AAO substrate's porous structure, with pore diameters measuring 250 ± 30 nm. The growth of MgO on the AAO substrate resulted in spherical structures, whose diameter expanded from 15 nm ± 3 nm to 1000 nm ± 250 nm with increasing MgCl concentration from the minor to major concentrations explored, respectively. X-ray photoelectron spectroscopy (XPS) analysis indicated that carbon serves as a linking agent between AAO and MgO within the composite. Notably, the composite synthesized with a 4 mM MgCl concentration exhibited the highest CO capture efficiency, as determined by UV-Vis absorbance studies using a sodium carbonate solution as the CO source. This efficiency was quantified with a 'k' constant of 0.10531, significantly higher than those of other studied samples. The superior performance of the 4 mM MgCl sample in CO capture is likely due to the optimal density of MgO structures formed on the sample's surface, enhancing its adsorptive capabilities as suggested by the XPS results.
PubMed: 38668152
DOI: 10.3390/nano14080658 -
Biochemia Medica Jun 2024This study aimed to examine whether the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) reference intervals for 19 commonly used biochemical...
INTRODUCTION
This study aimed to examine whether the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) reference intervals for 19 commonly used biochemical assays (potassium, sodium, chloride, calcium, magnesium, inorganic phosphorous, glucose, urea, creatinine, direct and total bilirubin, C-reactive protein (CRP), total protein, albumin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP) and lactate dehydrogenase (LD)) could be applied to the newborn population of one Croatian clinical hospital.
MATERIALS AND METHODS
Reference interval verification was performed according to the CLSI EP28-A3c guidelines. Samples of healthy newborns were selected using the direct sampling method and analyzed on the Beckman Coulter AU680 biochemical analyzer. If verification wasn't satisfactory, further procedure included determination of own reference intervals by analyzing 120 samples of healthy newborns.
RESULTS
After the first set of measurements, 14/19 tested reference intervals were adopted for use: calcium, inorganic phosphorous, glucose, urea, creatinine, total bilirubin, CRP, total protein, albumin, AST, ALT, GGT, ALP and LD. A second set of samples was tested for 5 analytes: potassium, sodium, chloride, magnesium and direct bilirubin. The verification results of the additional samples for sodium and chloride were satisfactory, while the results for potassium, magnesium and direct bilirubin remained unsatisfactory and new reference intervals were determined.
CONCLUSIONS
The CALIPER reference intervals can be implemented into routine laboratory and clinical practice for the tested newborn population for most of the analyzed assays, while own reference intervals for potassium, magnesium and direct bilirubin have been determined.
Topics: Humans; Infant, Newborn; Reference Values; Croatia; Bilirubin; Male; Female; C-Reactive Protein; Creatinine; Aspartate Aminotransferases; Alanine Transaminase; Blood Chemical Analysis; gamma-Glutamyltransferase; Alkaline Phosphatase; Potassium; Magnesium; L-Lactate Dehydrogenase; Chlorides; Calcium; Blood Glucose; Sodium
PubMed: 38665867
DOI: 10.11613/BM.2024.020705 -
Journal of Cardiothoracic Surgery Apr 2024St. Thomas cardioplegia is commonly administered to adults, yet repeated dosing at brief intervals is required. Del Nido's cardioplegic solution provides a prolonged... (Observational Study)
Observational Study Comparative Study
BACKGROUND
St. Thomas cardioplegia is commonly administered to adults, yet repeated dosing at brief intervals is required. Del Nido's cardioplegic solution provides a prolonged duration of safe myocardial arrest, yet it was primarily intended for pediatric cardiac surgery. Recently, there has been an increasing interest in using Del Nido's in adults; this might be due to its ease of administration and extended re-dosing intervals. This study contrasted Del Nido's to modified St. Thomas cardioplegia in adults.
METHODS
This study was conducted on 200 patients. Troponin-T was the primary outcome within the first 24 and 48 h post-surgery. Cardiopulmonary bypass time, cross-clamp time, intraoperative use of inotropic support, defibrillator and/or intra-aortic balloon were the secondary outcomes of the study.
RESULTS
There was a significant reduction in post-operative Troponin-T levels in the first 24 and 48 h within Del Nido's group compared to the modified St. Thomas group. The cross-clamp and cardiopulmonary bypass times were also found to be lower within Del Nido's group.
CONCLUSION
This study has demonstrated a significant reduction in early postoperative Troponin-T levels as well as operative times favoring Del Nido's in adults.
Topics: Humans; Heart Arrest, Induced; Retrospective Studies; Male; Female; Cardioplegic Solutions; Middle Aged; Cardiac Surgical Procedures; Troponin T; Adult; Cardiopulmonary Bypass; Aged; Potassium Chloride; Treatment Outcome; Mannitol; Sodium Bicarbonate; Bicarbonates; Solutions; Magnesium Sulfate; Calcium Chloride; Lidocaine; Electrolytes; Sodium Chloride; Magnesium
PubMed: 38664851
DOI: 10.1186/s13019-024-02683-1 -
Journal of Bacteriology May 2024The hypothesis was tested that a kinetical flow equilibrium of uptake and efflux reactions is responsible for balancing the cellular zinc content. The experiments were...
UNLABELLED
The hypothesis was tested that a kinetical flow equilibrium of uptake and efflux reactions is responsible for balancing the cellular zinc content. The experiments were done with the metal-resistant bacterium . In pulse-chase experiments, the cells were loaded with radioactive Zn and chased with the 100-fold concentration of non-radioactive zinc chloride. In parallel, the cells were loaded with isotope-enriched stable Zn and chased with non-enriched zinc to differentiate between zinc pools in the cell. The experiments demonstrated the existence of a kinetical flow equilibrium, resulting in a constant turnover of cell-bound zinc ions. The absence of the metal-binding cytoplasmic components, polyphosphate and glutathione, metal uptake, and metal efflux systems influenced the flow equilibrium. The experiments also revealed that not all zinc uptake and efflux systems are known in . Cultivation of the cells under zinc-replete, zinc-, and zinc-magnesium-starvation conditions influenced zinc import and export rates. Here, magnesium starvation had a stronger influence compared to zinc starvation. Other metal cations, especially cobalt, affected the cellular zinc pools and zinc export during the chase reaction. In summary, the experiments with Zn and Zn demonstrated a constant turnover of cell-bound zinc. This indicated that simultaneously occurring import and export reactions in combination with cytoplasmic metal-binding components resulted in a kinetical flow equilibrium that was responsible for the adjustment of the cellular zinc content.
IMPORTANCE
Understanding the biochemical action of a single enzyme or transport protein is the pre-requisite to obtain insight into its cellular function but this is only one half of the coin. The other side concerns the question of how central metabolic functions of a cell emerge from the interplay of different proteins and other macromolecules. This paper demonstrates that a flow equilibrium of zinc uptake and efflux reactions is at the core of cellular zinc homeostasis and identifies the most important contributors to this flow equilibrium: the uptake and efflux systems and metal-binding components of the cytoplasm.
Topics: Cupriavidus; Zinc; Biological Transport; Bacterial Proteins; Magnesium; Kinetics
PubMed: 38661374
DOI: 10.1128/jb.00080-24 -
Biological Trace Element Research Apr 2024Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder characterized by insulin resistance and chronic inflammation. Aerobic training (AT) and magnesium...
Impact of Combined Aerobic Training and Magnesium Supplementation on Serum Biomarkers and microRNA-155 and microRNA-21 Expression in Adipose Tissue of Type 2 Diabetic Rats: An Eight-Week Interventional Study.
BACKGROUND
Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder characterized by insulin resistance and chronic inflammation. Aerobic training (AT) and magnesium supplementation (Mg) have both been independently shown to have beneficial effects on glucose control and insulin sensitivity in individuals with T2DM. However, the potential synergistic effects of combining AT and Mg supplementation have not been extensively studied. This study aimed to investigate the effects of an 8-week AT and Mg supplementation on serum levels of insulin, glucose, leptin, adiponectin, TNF-α, IL-1β, IL-6, NF-κB, as well as the expression of mir-155 and mir-21 in the visceral adipose tissue (VAT) of rats with T2DM.
METHODS
For this experimental study, 32 male Wistar rats were induced with T2DM by a high-fat diet combined with a low-dose streptozotocin injection. The rats were randomly assigned to four groups: AT and Mg supplementation (AT + Mg), AT (5 days/week for 8 weeks), Mg supplementation (received daily supplementation of Mg chloride), and diabetic control (C). An 8-week AT program was implemented, with gradually increasing the intensity and duration to reach 25 m/min and 60 min in the 8th week, respectively. The training intensity was set at 50-60% of VO2max. The Mg groups were provided with rat diets containing 1000 mg/kg of Mg. The AT + Mg group received both interventions, while the C group served as the untreated control. Serum biomarkers were measured using enzyme-linked immunosorbent assay (ELISA), and VAT samples were collected for gene expression analysis using real-time polymerase chain reaction (PCR).
RESULTS
Serum biomarker analysis revealed that the AT + Mg group had a significant decrease in fasting insulin (p = 0.001) and serum glucose (p = 0.001), as well as an increase in adiponectin levels compared to the C group (p = 0.002). Additionally, the AT + Mg group showed a significant reduction in serum leptin, TNF-α, IL-6, IL-1β, and NF-κB, as well as downregulation of mir-155 and mir-21 in the VAT compared to the other groups. The AT group also showed improvements in several parameters, while the Mg group had fewer significant differences compared to the C group.
CONCLUSION
The combination of AT and Mg supplementation provides a synergistic effect that improves serum biomarkers and downregulates pro-inflammatory microRNAs in the VAT of T2DM rats. Meanwhile, Mg supplementation alone does not have a significant effect on pro-inflammatory microRNAs in the VAT. These findings suggest that such combined interventions could be a promising strategy for managing T2DM, potentially ameliorating inflammatory states and improving metabolic health.
PubMed: 38658451
DOI: 10.1007/s12011-024-04186-5