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The New England Journal of Medicine Mar 2022Whether the use of balanced multielectrolyte solution (BMES) in preference to 0.9% sodium chloride solution (saline) in critically ill patients reduces the risk of acute... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Whether the use of balanced multielectrolyte solution (BMES) in preference to 0.9% sodium chloride solution (saline) in critically ill patients reduces the risk of acute kidney injury or death is uncertain.
METHODS
In a double-blind, randomized, controlled trial, we assigned critically ill patients to receive BMES (Plasma-Lyte 148) or saline as fluid therapy in the intensive care unit (ICU) for 90 days. The primary outcome was death from any cause within 90 days after randomization. Secondary outcomes were receipt of new renal-replacement therapy and the maximum increase in the creatinine level during ICU stay.
RESULTS
A total of 5037 patients were recruited from 53 ICUs in Australia and New Zealand - 2515 patients were assigned to the BMES group and 2522 to the saline group. Death within 90 days after randomization occurred in 530 of 2433 patients (21.8%) in the BMES group and in 530 of 2413 patients (22.0%) in the saline group, for a difference of -0.15 percentage points (95% confidence interval [CI], -3.60 to 3.30; P = 0.90). New renal-replacement therapy was initiated in 306 of 2403 patients (12.7%) in the BMES group and in 310 of 2394 patients (12.9%) in the saline group, for a difference of -0.20 percentage points (95% CI, -2.96 to 2.56). The mean (±SD) maximum increase in serum creatinine level was 0.41±1.06 mg per deciliter (36.6±94.0 μmol per liter) in the BMES group and 0.41±1.02 mg per deciliter (36.1±90.0 μmol per liter) in the saline group, for a difference of 0.01 mg per deciliter (95% CI, -0.05 to 0.06) (0.5 μmol per liter [95% CI, -4.7 to 5.7]). The number of adverse and serious adverse events did not differ meaningfully between the groups.
CONCLUSIONS
We found no evidence that the risk of death or acute kidney injury among critically ill adults in the ICU was lower with the use of BMES than with saline. (Funded by the National Health and Medical Research Council of Australia and the Health Research Council of New Zealand; PLUS ClinicalTrials.gov number, NCT02721654.).
Topics: Acute Kidney Injury; Adult; Aged; Critical Care; Critical Illness; Double-Blind Method; Female; Fluid Therapy; Gluconates; Humans; Intensive Care Units; Magnesium Chloride; Male; Middle Aged; Potassium Chloride; Saline Solution; Sodium Acetate; Sodium Chloride; Treatment Outcome
PubMed: 35041780
DOI: 10.1056/NEJMoa2114464 -
Materials Today. Bio Dec 2022Implantation of cardiovascular stents is an important therapeutic method to treat coronary artery diseases. Bare-metal and drug-eluting stents show promising clinical... (Review)
Review
Implantation of cardiovascular stents is an important therapeutic method to treat coronary artery diseases. Bare-metal and drug-eluting stents show promising clinical outcomes, however, their permanent presence may create complications. In recent years, numerous preclinical and clinical trials have evaluated the properties of bioresorbable stents, including polymer and magnesium-based stents. Three-dimensional (3D) printed-shape-memory polymeric materials enable the self-deployment of stents and provide a novel approach for individualized treatment. Novel bioresorbable metallic stents such as iron- and zinc-based stents have also been investigated and refined. However, the development of novel bioresorbable stents accompanied by clinical translation remains time-consuming and challenging. This review comprehensively summarizes the development of bioresorbable stents based on their preclinical/clinical trials and highlights translational research as well as novel technologies for stents (e.g., bioresorbable electronic stents integrated with biosensors). These findings are expected to inspire the design of novel stents and optimization approaches to improve the efficacy of treatments for cardiovascular diseases.
PubMed: 35937578
DOI: 10.1016/j.mtbio.2022.100368 -
Nutrients May 2022Patients suffering from fibromyalgia often report stress and pain, with both often refractory to usual drug treatment. Magnesium supplementation seems to improve... (Randomized Controlled Trial)
Randomized Controlled Trial
Patients suffering from fibromyalgia often report stress and pain, with both often refractory to usual drug treatment. Magnesium supplementation seems to improve fibromyalgia symptoms, but the level of evidence is still poor. This study is a randomized, controlled, double-blind trial in fibromyalgia patients that compared once a day oral magnesium 100 mg (Chronomag, magnesium chloride technology formula) to placebo, for 1 month. The primary endpoint was the level of stress on the DASS-42 scale, and secondary endpoints were pain, sleep, quality of life, fatigue, catastrophism, social vulnerability, and magnesium blood concentrations. After 1 month of treatment, the DASS-42 score decreased in the magnesium and placebo groups but not significantly (21.8 ± 9.6 vs. 21.6 ± 10.8, respectively, = 0.930). Magnesium supplementation significantly reduced the mild/moderate stress subgroup (DASS-42 stress score: 22.1 ± 2.8 to 12.3 ± 7.0 in magnesium vs. 21.9 ± 11.9 to 22.9 ± 11.9 in placebo, = 0.003). Pain severity diminished significantly ( = 0.029) with magnesium while the other parameters were not significantly different between both groups. These findings show, for the first time, that magnesium improves mild/moderate stress and reduces the pain experience in fibromyalgia patients. This suggests that daily magnesium could be a useful treatment to improve the burden of disease of fibromyalgia patients and calls for a larger clinical trial.
Topics: Fibromyalgia; Humans; Magnesium; Magnesium Chloride; Pain; Quality of Life
PubMed: 35631229
DOI: 10.3390/nu14102088 -
IBRO Reports Jun 2020The technical difficulty to isolate microglia, astrocytes and infiltrating immune cells from mouse brain is nowadays a limiting factor in the study of neuroinflammation....
The technical difficulty to isolate microglia, astrocytes and infiltrating immune cells from mouse brain is nowadays a limiting factor in the study of neuroinflammation. Brain isolation requirements are cell-type and animal-age dependent, but current brain dissociation procedures are poorly standardized. This lack of comprehensive studies hampers the selection of optimized methodologies. Thus, we present here a comparative analysis of dissociation methods and Percoll-based separation to identify the most efficient procedure for the combined isolation of healthy microglia, astrocytes and infiltrated leukocytes; distinguishing neonatal and adult mouse brain. Gentle mechanical dissociation and DNase I incubation was supplemented with papain or collagenase II. Dispase II digestion was also used alone or in combination. In addition, cell separation efficiency of 30 % and 30-70 % Percoll gradients was compared. In these experiments, cell yield and integrity of freshly dissociated cells was measured by flow cytometry. We found that papain digestion in combination with dispase II followed by 30 % Percoll separation is the most balanced method to obtain a mixture of microglia, astrocytes and infiltrated immune cells; while addition of dispase II was not an advantage for neonatal brain. These dissociation conditions allowed flow cytometry detection of a slight glial activation triggered by sublethal LPS injection. In conclusion, the enzymes and Percoll density gradients tested here affected differently resting microglia, activated microglia/macrophages, astrocytes and infiltrated lymphocytes. Also, newborn and adult brain showed contrasting reactions to digestion. Our study highlights the strength of flow cytometry for the simultaneous analysis of neuroimmune cell populations once extraction is optimized.
PubMed: 32215337
DOI: 10.1016/j.ibror.2019.12.004 -
Journal of Dairy Science Jun 2022The aim of this study was to manufacture magnesium-fortified Chihuahua cheese and to evaluate the effect of magnesium fortification on quality parameters. Addition of...
The aim of this study was to manufacture magnesium-fortified Chihuahua cheese and to evaluate the effect of magnesium fortification on quality parameters. Addition of magnesium chloride to milk during pasteurization (5.44, 10.80, 16.40, 22.00, and 25.20 g of MgCl·6HO/L of milk) resulted in cheese with increased magnesium content, proportional to the amount of magnesium added (up to 2,957.13 mg of Mg/kg of cheese). As magnesium content increased, coagulation time and moisture content also increased, whereas calcium content decreased. Higher levels of magnesium fortification (16.40 g of MgCl·6HO/L of milk or more) induced the development of bitter-acid flavors and softer texture. Addition of 10.80 g of MgCl·6HO/L to milk resulted in Chihuahua cheese that meets regulatory standards and possesses physicochemical and sensory characteristics similar to those of nonfortified Chihuahua cheese. Under this milk fortification level, the manufactured cheese is able to provide 148.4 mg of magnesium per day (35% of the recommended daily intake of magnesium for adult males and 46% for adult females) assuming 3 portions (28 g each) are consumed.
Topics: Animals; Cheese; Magnesium; Milk; Taste
PubMed: 35346481
DOI: 10.3168/jds.2021-21631 -
The Veterinary Clinics of North... Aug 2021Barbiturate overdose as a method of euthanasia is becoming unacceptable. This has made alternative methods of euthanasia very important. Gunshot or captive bolt... (Review)
Review
Barbiturate overdose as a method of euthanasia is becoming unacceptable. This has made alternative methods of euthanasia very important. Gunshot or captive bolt euthanasia is among methods that are acceptable, but they may not be esthetically acceptable. This has led to the use of other methods of euthanasia. Inducing anesthesia prior to euthanasia offers an easier method of control. Adjunctive techniques using intravenous potassium or magnesium salts administered intravenously and intracardiac administration of potassium chloride or intrathecal lidocaine offer alternatives that work well and are more environmentally safer than barbiturates. Pithing and exsanguination are also environmentally safer but may not be as esthetically acceptable as the other methods.
Topics: Animals; Barbiturates; Euthanasia, Animal; Horse Diseases; Horses; Lidocaine; Magnesium Chloride; Potassium Chloride
PubMed: 34243883
DOI: 10.1016/j.cveq.2021.04.014 -
American Journal of Translational... 2022Gitelman syndrome (GS) is an autosomal recessive salt-losing tubulopathy caused by biallelic inactivating mutations in the SLC12A3 gene. This gene encodes the... (Review)
Review
Gitelman syndrome (GS) is an autosomal recessive salt-losing tubulopathy caused by biallelic inactivating mutations in the SLC12A3 gene. This gene encodes the thiazide-sensitive sodium-chloride cotransporter (NCC) which is exclusively expressed in the distal convoluted tubules (DCT). GS patients classically present with hypokalemic metabolic alkalosis with hypocalciuria and hypomagnesemia. While hypokalemia and metabolic alkalosis are easily explained by effects of the genotypic defect in GS, the mechanisms by which hypomagnesemia and hypocalciuria develop in GS are poorly understood. In this review, we aim to achieve three major objectives. First, present a concise discussion about current understanding on physiologic calcium and magnesium handling in the DCT. Second, integrate expression data from studies on calciotropic and magnesiotropic proteins relevant to the GS disease state. Lastly, provide insights into the possible mechanisms of calcium-magnesium crosstalk relating to the co-occurrence of hypocalciuria and hypomagnesemia in GS models. Our analyses highlight specific areas of study that are valuable in elucidating possible molecular pathways of hypocalciuria and hypomagnesemia in GS.
PubMed: 35173827
DOI: No ID Found -
Acta Crystallographica. Section F,... Jul 2020Succinyl-CoA synthetase (SCS) catalyzes the only substrate-level phosphorylation step in the tricarboxylic acid cycle. Human GTP-specific SCS (GTPSCS), an...
Succinyl-CoA synthetase (SCS) catalyzes the only substrate-level phosphorylation step in the tricarboxylic acid cycle. Human GTP-specific SCS (GTPSCS), an αβ-heterodimer, was produced in Escherichia coli. The purified protein crystallized from a solution containing tartrate, CoA and magnesium chloride, and a crystal diffracted to 1.52 Å resolution. Tartryl-CoA was discovered to be bound to GTPSCS. The CoA portion lies in the amino-terminal domain of the α-subunit and the tartryl end extends towards the catalytic histidine residue. The terminal carboxylate binds to the phosphate-binding site of GTPSCS.
Topics: Amino Acid Sequence; Binding Sites; Coenzyme A; Crystallography, X-Ray; Dimerization; Escherichia coli; Guanosine Triphosphate; Histidine; Humans; Magnesium Chloride; Models, Molecular; Phosphates; Phosphorylation; Protein Binding; Protein Conformation; Protein Domains; Recombinant Proteins; Succinate-CoA Ligases; Tartrates
PubMed: 32627745
DOI: 10.1107/S2053230X20008201