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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 -
Canine and feline foetal fluids: Volume, hormonal and biochemical characterization during pregnancy.Veterinary Medicine and Science May 2024This study aimed to evaluate the volume, the concentration of steroid hormones, and biochemical composition of the foetal fluids at different gestational ages in dogs...
BACKGROUND AND OBJECTIVES
This study aimed to evaluate the volume, the concentration of steroid hormones, and biochemical composition of the foetal fluids at different gestational ages in dogs and cats.
METHODS
Following the ovariohysterectomy, the allantoic and amniotic fluid samples were collected from pregnant bitches and queens and were assigned to different groups according to their gestational age.
RESULTS
The canine and feline allantoic fluid volume increased during pregnancy, reached its maximum values on days 40-49 and then decreased. The canine and feline amniotic fluid volume increased steadily by the last days of pregnancy. In spite of significant changes of sex hormones in the foetal fluids, their concentration and ratios were not significantly different between male and female fetuses. The canine amniotic cortisol concentration increased until days 40-49 and decreased significantly afterwards. The maximum cortisol concentrations in the feline allantoic and amniotic fluids were observed on days 50-60 and 40-49, respectively. During the canine pregnancy, the concentrations of calcium, phosphorus, chloride, sodium, triglyceride, cholesterol, total protein, albumin and the activities of aminotransferase (AST), alkaline phosphatase (ALP), amylase and gamma-glutamyl transferase (GGT) in the amniotic fluid were higher than the allantoic fluid. The magnesium, potassium, lactate dehydrogenase (LDH) activity, creatine and lipase were higher in the allantoic fluid. In the feline allantoic fluid, potassium, magnesium, phosphorus, creatinine, albumin and glucose concentrations and the activities of creatine kinase (CK), GGT, LDH and lipase were higher. The ALP, AST activities, sodium and calcium concentrations were higher in the amniotic fluid (p < 0.05).
CONCLUSION
Volume of foetal fluids was determined in dogs and cats. Concentration of sex hormones did not different between male and female fetuses.
Topics: Animals; Cats; Dogs; Female; Pregnancy; Amniotic Fluid; Male; Pregnancy, Animal; Gestational Age; Hydrocortisone; Allantois
PubMed: 38654677
DOI: 10.1002/vms3.1452 -
The Journal of Physical Chemistry. B Apr 2024Complex molten chloride salt mixtures of uranium, magnesium, and sodium are top candidates for promising nuclear energy technologies to produce electricity based on...
Complex molten chloride salt mixtures of uranium, magnesium, and sodium are top candidates for promising nuclear energy technologies to produce electricity based on molten salt reactors. From a local structural perspective, LaCl is similar to UCl and hence a good proxy to study these complex salt mixtures. As fission products, lanthanide salts and their mixtures are also very important in their own right. This article describes from an experimental and theory perspective how very different the structural roles of MgCl and NaCl are in mixtures with LaCl. We find that, whereas MgCl becomes an integral part of multivalent ionic networks, NaCl separates them. In a recent article ( , , 21751-21762) we have called the disruptive behavior of NaCl "the spacer salt effect". Because of the heterogeneous nature of these salt mixtures, there are multiple structural motifs in the melt, each with its particular free energetics. Our work identifies and quantifies these; it also elucidates the mechanisms through which Cl ions exchange between Mg-rich and La-rich environments.
PubMed: 38624173
DOI: 10.1021/acs.jpcb.4c01429 -
International Journal of Molecular... Apr 2024Salt is frequently introduced in ecosystems, where it acts as a pollutant. This study examined how changes in salinity affect the survival and development of zebrafish...
Salt is frequently introduced in ecosystems, where it acts as a pollutant. This study examined how changes in salinity affect the survival and development of zebrafish from the two-cell to the blastocyst stage and from the blastocyst to the larval stage. Control zebrafish embryos were cultured in E3 medium containing 5 mM Sodium Chloride (NaCl), 0.17 mM Potassium Chloride (KCL), 0.33 mM Calcium Chloride (CaCl), and 0.33 mM Magnesium Sulfade (MgSO). Experiments were conducted using increasing concentrations of each individual salt at 5×, 10×, 50×, and 100× the concentration found in E3 medium. KCL, CaCl, and MgSO did not result in lethal abnormalities and did not affect early embryo growth at any of the concentrations tested. Concentrations of 50× and 100× NaCl caused embryonic death in both stages of development. Concentrations of 5× and 10× NaCl resulted in uninflated swim bladders in 12% and 65% of larvae, compared to 4.2% of controls, and caused 1654 and 2628 genes to be differentially expressed in blastocysts, respectively. The ATM signaling pathway was affected, and the Sonic Hedgehog pathway genes Shh and Ptc1 implicated in swim bladder development were downregulated. Our findings suggest that increased NaCl concentrations may alter gene expression and cause developmental abnormalities in animals found in affected ecosystems.
Topics: Animals; Hedgehog Proteins; Sodium Chloride; Water; Zebrafish; Calcium Chloride; Ecosystem; Sodium Chloride, Dietary; Larva; Perciformes; Gene Expression
PubMed: 38612913
DOI: 10.3390/ijms25074104 -
Medicine Apr 2024Gitelman syndrome (GS), also known as familial hypokalemia and hypomagnesemia, is a rare autosomal recessive inherited disease caused by primary renal desalinization...
RATIONALE
Gitelman syndrome (GS), also known as familial hypokalemia and hypomagnesemia, is a rare autosomal recessive inherited disease caused by primary renal desalinization caused by impaired reabsorption of sodium and chloride ions in the distal renal tubules. We report a case of clinical and genetic characteristics of GS accompanied with Graves disease and adrenocorticotrophic hormone (ACTH)-independent adrenocortical adenoma.
PATIENT CONCERNS
The patient is a 45 year old female, was admitted to our hospital, due to a left adrenal gland occupying lesion as the chief complaint.
DIAGNOSIS
The patient was finally diagnosed as GS with Graves disease and adrenocortical adenoma.
INTERVENTIONS
Potassium magnesium aspartate (1788 mg/d, taken orally 3 times a day (supplement a few times a day, intake method, treatment duration). Contains 217.2 mg of potassium and 70.8 mg of magnesium, and potassium chloride (4.5 g/d, taken orally 3 times a day (supplement a few times a day, intake method, and treatment duration); Potassium 2356 mg), spironolactone (20 mg/d, taken orally once a day (supplement a few times a day, intake method, treatment duration). After 3 months of treatment, the patient's blood potassium fluctuated between 3.3-3.6 mmol/L, and blood magnesium fluctuated between 0.5-0.7 mmol/L, indicating a relief of fatigue symptoms.
OUTCOMES
On the day 6 of hospitalization, the symptoms of dizziness, limb fatigue, fatigue and pain were completely relieved on patient. In the follow-up of the following year, no recurrence of the condition was found.
LESSONS
The novel c.1444-10(IVS11)G > A variation may be a splicing mutation. The compound heterozygous mutations of the SLC12A3 gene may be the pathogenic cause of this GS pedigree.
Topics: Female; Humans; Middle Aged; Gitelman Syndrome; Adrenocortical Adenoma; Magnesium; Graves Disease; Fatigue; Potassium; Solute Carrier Family 12, Member 3
PubMed: 38608089
DOI: 10.1097/MD.0000000000037770