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Hypertension (Dallas, Tex. : 1979) Dec 2023Thiazide diuretics (TD) are the first-line treatment of hypertension because of its consistent benefit in lowering blood pressure and cardiovascular risk. TD is also... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Thiazide diuretics (TD) are the first-line treatment of hypertension because of its consistent benefit in lowering blood pressure and cardiovascular risk. TD is also known to cause an excess risk of diabetes, which may limit long-term use. Although potassium (K) depletion was thought to be the main mechanism of TD-induced hyperglycemia, TD also triggers magnesium (Mg) depletion. However, the role of Mg supplementation in modulating metabolic side effects of TD has not been investigated. Therefore, we aim to determine the effect of potassium magnesium citrate (KMgCit) on fasting plasma glucose and liver fat by magnetic resonance imaging during TD therapy.
METHODS
Accordingly, we conducted a double-blinded RCT in 60 nondiabetic hypertension patients to compare the effects of KCl versus KMgCit during chlorthalidone treatment. Each patient received chlorthalidone alone for 3 weeks before randomization. Primary end point was the change in fasting plasma glucose after 16 weeks of KCl or KMgCit supplementation from chlorthalidone alone.
RESULTS
The mean age of subjects was 59±11 years (30% Black participants). Chlorthalidone alone induced a significant rise in fasting plasma glucose, and a significant fall in serum K, serum Mg, and 24-hour urinary citrate excretion (all <0.05). KMgCit attenuated the rise in fasting plasma glucose by 7.9 mg/dL versus KCl (<0.05), which was not observed with KCl. There were no significant differences in liver fat between the 2 groups.
CONCLUSIONS
KMgCit is superior to KCl, the common form of K supplement used in clinical practice, in preventing TD-induced hyperglycemia. This action may improve tolerability and cardiovascular safety in patients with hypertension treated with this drug class.
Topics: Aged; Humans; Middle Aged; Antihypertensive Agents; Blood Glucose; Blood Pressure; Chlorthalidone; Citrates; Hyperglycemia; Hypertension; Potassium; Potassium Chloride; Sodium Chloride Symporter Inhibitors
PubMed: 37846572
DOI: 10.1161/HYPERTENSIONAHA.123.21932 -
Nephrology, Dialysis, Transplantation :... May 2024Calcineurin inhibitors affect kidney electrolyte handling and blood pressure through an effect on the distal tubule. The second generation calcineurin inhibitor...
BACKGROUND AND HYPOTHESIS
Calcineurin inhibitors affect kidney electrolyte handling and blood pressure through an effect on the distal tubule. The second generation calcineurin inhibitor voclosporin causes hypomagnesemia and hypercalciuria less often than tacrolimus. This suggests different effects on the distal tubule, but this has not yet been investigated experimentally.
METHODS
Rats were treated with voclosporin, tacrolimus or vehicle for 28 days. Dosing was based on a pilot experiment to achieve clinically therapeutic concentrations. Drug effects were assessed by electrolyte handling at day 18 and 28, thiazide testing at day 20, telemetric blood pressure recordings, and analysis of mRNA and protein levels of distal tubular transporters at day 28.
RESULTS
Compared to vehicle, tacrolimus but not voclosporin significantly increased the fractional excretions of calcium (>4-fold), magnesium and chloride (both 1.5-fold) and caused hypomagnesemia. Tacrolimus but not voclosporin significantly reduced distal tubular transporters at mRNA and/or protein level, including the sodium-chloride cotransporter, transient receptor melastatin 6, transient receptor potential vanilloid 5, cyclin M2, sodium-calcium exchanger and calbindin-D28K. Tacrolimus but not voclosporin reduced the mRNA level and urinary excretion of epidermal growth factor. The saluretic response to hydrochlorothiazide at day 20 was similar in the voclosporin and vehicle groups, whereas it was lower in the tacrolimus group. The phosphorylated form of the sodium-chloride cotransporter was significantly higher at day 28 in rats treated with voclosporin than in those treated with tacrolimus. Tacrolimus transiently increased blood pressure, whereas voclosporin caused a gradual but persistent increase in blood pressure which was further characterized by high renin, normal aldosterone, and low endothelin-1.
CONCLUSIONS
In contrast to tacrolimus, voclosporin does not cause hypercalciuria and hypomagnesemia, but similarly causes hypertension. Our data reveal differences between the distal tubular effects of tacrolimus and voclosporin and provide a pathophysiological basis for the clinically observed differences between the two calcineurin inhibitors.
PubMed: 38777623
DOI: 10.1093/ndt/gfae119 -
3 Biotech Jan 2024Nano-PCR is a potential tool for the early detection of plant viruses. In the current study, different concentrations of silver nanoparticles (20 nm) and magnesium...
UNLABELLED
Nano-PCR is a potential tool for the early detection of plant viruses. In the current study, different concentrations of silver nanoparticles (20 nm) and magnesium oxide nanoparticles (50 nm) were included in the PCR mixture to improve the sensitivity of PCR for the detection of tomato leaf curl virus. The inclusion of nanoparticles in single or combination in PCR mixture has resulted in improvement of PCR sensitivity. Four-fold improvement was exhibited by the inclusion of 3 ng/µL silver nanoparticles, whereas the combination of silver and magnesium oxide nanoparticles (3 ng/µL and 200 ng/µL, respectively), resulted in a 4.5-fold improvement. The inclusion of 200 ng/µL of magnesium oxide nanoparticles in the PCR mixture exhibited a 7.6-fold increase in PCR sensitivity. Replacement of magnesium chloride with a combination of silver and magnesium oxide nanoparticles (3 ng/µL and 275 ng/µL, respectively) resulted in a 12-fold increase. A 13-fold improvement in PCR sensitivity was observed by the replacement of magnesium chloride in PCR buffer with 275 ng/µL of magnesium oxide nanoparticles. This could also produce detectable amplicon in PCR with a minimum of 25 cycles, resulting in a 26.5% reduction in the duration of PCR. This is the first report on the use of magnesium oxide nanoparticles in PCR for the early detection and better management of tomato leaf curl virus.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s13205-023-03842-2.
PubMed: 38074290
DOI: 10.1007/s13205-023-03842-2 -
JAMA Network Open May 2024Understanding the effect of antenatal magnesium sulfate (MgSO4) treatment on functional connectivity will help elucidate the mechanism by which it reduces the risk of... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Understanding the effect of antenatal magnesium sulfate (MgSO4) treatment on functional connectivity will help elucidate the mechanism by which it reduces the risk of cerebral palsy and death.
OBJECTIVE
To determine whether MgSO4 administered to women at risk of imminent preterm birth at a gestational age between 30 and 34 weeks is associated with increased functional connectivity and measures of functional segregation and integration in infants at term-equivalent age, possibly reflecting a protective mechanism of MgSO4.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study was nested within a randomized placebo-controlled trial performed across 24 tertiary maternity hospitals. Participants included infants born to women at risk of imminent preterm birth at a gestational age between 30 and 34 weeks who participated in the MAGENTA (Magnesium Sulphate at 30 to 34 Weeks' Gestational Age) trial and underwent magnetic resonance imaging (MRI) at term-equivalent age. Ineligibility criteria included illness precluding MRI, congenital or genetic disorders likely to affect brain structure, and living more than 1 hour from the MRI center. One hundred and fourteen of 159 eligible infants were excluded due to incomplete or motion-corrupted MRI. Recruitment occurred between October 22, 2014, and October 25, 2017. Participants were followed up to 2 years of age. Analysis was performed from February 1, 2021, to February 27, 2024. Observers were blind to patient groupings during data collection and processing.
EXPOSURES
Women received 4 g of MgSO4 or isotonic sodium chloride solution given intravenously over 30 minutes.
MAIN OUTCOMES AND MEASURES
Prior to data collection, it was hypothesized that infants who were exposed to MgSO4 would show enhanced functional connectivity compared with infants who were not exposed.
RESULTS
A total of 45 infants were included in the analysis: 24 receiving MgSO4 treatment and 21 receiving placebo; 23 (51.1%) were female and 22 (48.9%) were male; and the median gestational age at scan was 40.0 (IQR, 39.1-41.1) weeks. Treatment with MgSO4 was associated with greater voxelwise functional connectivity in the temporal and occipital lobes and deep gray matter structures and with significantly greater clustering coefficients (Hedge g, 0.47 [95% CI, -0.13 to 1.07]), transitivity (Hedge g, 0.51 [95% CI, -0.10 to 1.11]), local efficiency (Hedge g, 0.40 [95% CI, -0.20 to 0.99]), and global efficiency (Hedge g, 0.31 [95% CI, -0.29 to 0.90]), representing enhanced functional segregation and integration.
CONCLUSIONS AND RELEVANCE
In this cohort study, infants exposed to MgSO4 had greater voxelwise functional connectivity and functional segregation, consistent with increased brain maturation. Enhanced functional connectivity is a possible mechanism by which MgSO4 protects against cerebral palsy and death.
Topics: Humans; Magnesium Sulfate; Female; Pregnancy; Infant, Newborn; Magnetic Resonance Imaging; Male; Adult; Gestational Age; Cohort Studies; Premature Birth; Infant; Brain; Prenatal Care; Cerebral Palsy
PubMed: 38805222
DOI: 10.1001/jamanetworkopen.2024.13508 -
Plants (Basel, Switzerland) May 2024The current investigation aims to underline the impact of salicylic acid or calcium chloride seed pre-treatments on mineral status and oxidative stress markers, namely...
Salicylic Acid and Calcium Chloride Seed Priming: A Prominent Frontier in Inducing Mineral Nutrition Balance and Antioxidant System Capacity to Enhance the Tolerance of Barley Plants to Salinity.
The current investigation aims to underline the impact of salicylic acid or calcium chloride seed pre-treatments on mineral status and oxidative stress markers, namely levels of electrolyte leakage (EL) and lipid peroxidation levels, measured as thiobarbituric reactive substances (TBARS), and the activity of some antioxidant enzymes in roots and leaves of plants in two barley species grown under various salt treatments. Overall, our results revealed that salinity inhibits essential nutrient absorption such as iron, calcium, magnesium and potassium and stimulates the absorption of sodium. Also, this environmental constraint induced oxidative stress in plants in comparison with the control conditions. This state of oxidative stress is reflected by an increase in TBARS content as well as the stimulation of EL values. In addition, salinity induced disturbances in the activity of antioxidant enzymes, which were mainly dependent on the applied salt concentration and the species. In addition, maintained high antioxidant enzyme activity and low levels of oxidative stress parameters, which reinforces its salt-tolerant character. Importantly, salicylic acid or calcium chloride seed priming alleviated the mineral imbalance and the oxidative damage induced by salinity. Moreover, seed priming improves iron, calcium magnesium and potassium content and limitsthe accumulation of sodium. Also, both treatments not only decrease TBARS levels and limit EL, but they also stimulate the antioxidant enzyme activities in the leaves and roots of the stressed plants as compared with stressed plants grown from non-primed seeds. Interestingly, the beneficial effects of the mentioned treatments were more notable on species.
PubMed: 38732483
DOI: 10.3390/plants13091268 -
Journal of Palliative Medicine Dec 2023Peripheral neuropathy is common in chronic kidney disease (CKD) and may be multifactorial in origin, resulting from uremia, hyperkalemia, and diabetes. Previous studies... (Clinical Trial)
Clinical Trial
Peripheral neuropathy is common in chronic kidney disease (CKD) and may be multifactorial in origin, resulting from uremia, hyperkalemia, and diabetes. Previous studies have suggested that magnesium plays a crucial role in chronic pain. Studies evaluating magnesium in neuropathy have demonstrated mixed results. To provide preliminary data on the effectiveness of transdermal magnesium in treating peripheral neuropathy related to CKD. Twenty participants with advanced CKD were enrolled from a major teaching hospital clinic in Sydney, Australia. Each participant was provided with a spray bottle containing magnesium chloride and instructed to apply five sprays to each limb affected by neuropathy daily for 12 weeks. Participants completed the Neuropathy Total Symptom Score-6 (NTSS-6) every 4 weeks during follow-up. Serum magnesium concentrations were measured at 4-week intervals. Twenty participants were recruited, of which 14 completed the 12-week follow-up period. Mean age was 78.90 years, 80.00% were female and mean estimated glomerular filtration rate was 9.78 mL/min/1.73 m. With intention to treat analysis (mean [95% confidence interval]), NTSS-6 was significantly reduced at weeks 8 (4.04 [2.43-5.65]) and 12 (4.26 [2.47-6.05]), compared with baseline (6.92 [5.29-8.55]), < 0.05. Serum magnesium concentration did not change significantly during the study. This pilot study suggests that transdermal magnesium may be beneficial in reducing frequency and severity of peripheral neuropathic symptoms in patients with advanced CKD. australianclinicaltrials.gov.au. Identifier: ACTRN12621000841875. Date first registered January 7, 2021.
Topics: Aged; Female; Humans; Male; Administration, Cutaneous; Magnesium; Peripheral Nervous System Diseases; Pilot Projects; Renal Insufficiency, Chronic
PubMed: 37486715
DOI: 10.1089/jpm.2023.0229 -
Veterinary Sciences Jul 2023Giant Pacific octopuses () (GPOs) are commonly housed in zoos or aquaria, and sedation, anesthesia, and/or euthanasia may be indicated for a variety of reasons. Despite...
Giant Pacific octopuses () (GPOs) are commonly housed in zoos or aquaria, and sedation, anesthesia, and/or euthanasia may be indicated for a variety of reasons. Despite this need, evidence-based data on best practices is limited and focuses on smaller or more tropical species. The objectives of this study were to survey the aquatic community regarding the husbandry and veterinary care of GPOs, with a specific focus on anesthetic and euthanasia protocols. A two-part web-based survey was distributed to four aquatic and/or veterinary email listservs. Individuals from fifty-two institutions participated in phase one. Results documented that 40 (78 percent) participating institutions currently house GPOs, with most housing one and nine institutions housing two to three GPOs. The median (range) habitat volume is 5405 (1893-16,465) L, and 78 percent of systems are closed. Of the institutions surveyed, 23 have anesthetized or sedated a GPO for nonterminal procedures, including wound care, biopsies, and hemolymph collection. Reported methods of sedation or anesthesia include magnesium chloride, ethanol, isoflurane, tricaine methanesulfonate (MS-222), magnesium sulfate, benzocaine, and dexmedetomidine. Drugs or methods used for euthanasia include magnesium chloride, ethanol, mechanical decerebration, pentobarbital, isoflurane, MS-222, magnesium sulfate, benzocaine, potassium chloride, dexmedetomidine, and freezing. Reported observed side effects include ineffectiveness or inadequate sedation, inking, prolonged drug effects, and behavior changes. Survey data have the potential to guide the husbandry and veterinary care of GPOs and build the framework for future prospective studies on GPO sedation and anesthesia.
PubMed: 37505853
DOI: 10.3390/vetsci10070448 -
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 -
PloS One 2023The aim of this study is to evaluate the synergistic effect of polyester fiber-reinforced and nanoslica on the technical performance and durability of geopolymer mortar...
The aim of this study is to evaluate the synergistic effect of polyester fiber-reinforced and nanoslica on the technical performance and durability of geopolymer mortar in terms of the chemical resistance. The study examined how the addition of polyester fiber and nanosilica affects the short-term severe durability of geopolymer mortar specimens made with fly ash (type F). The specimens were cured under ambient conditions. Different percentages (0.6%, 1.2%, and 1.8%) of polyester fiber were used, both with and without nanosilica. Additionally, a reference mixture containing only nanosilica was prepared.All mixtures had a liquid to binder ratio of 0.50, and the ratio of NaOH to Na2SiO3 solution was kept at 2.5:1 by weight. The produced mixes, after 28 days of ambient curing, were immersed for another 28 days in solutions containing 3.5%, 5%, and 5% of sodium chloride, magnesium sulphate and sulfuric acid, respectively. For comparison, control specimens which were not exposed to chemical attacks were tested at the same age of 56 days. Moreover, water absorption and sorptivity tests were conducted to explain the durability performance in a more detailed way. The test results express that the combination of both materials showed a synergistic effect and resulted in greater improvements in compressive and flexural strengths. Both materials can reduce the reduction in compressive strength caused by sulfuric acid exposure, but polyester fiber can increase mass loss. The presence of magnesium sulfate and sodium chloride can lead to a reduction in strength, but the addition of both polyester fiber and nanosilica can mitigate these effects. The addition of fibers creates a network of pores that can limit water absorption, and nanosilica can further enhance the microstructure and reduce water absorption. However, using polyester fiber beyond 1.2 percent can adversely affect the rate of water absorption.
Topics: Sulfuric Acids; Coal Ash; Compressive Strength; Magnesium Sulfate; Polyesters; Silicon Dioxide; Sodium Chloride
PubMed: 37751445
DOI: 10.1371/journal.pone.0289497 -
Frontiers in Veterinary Science 2023This study aimed to establish baseline variables for calves transported by road and ferry from Ireland to the Netherlands and to investigate the effect of journey [two...
This study aimed to establish baseline variables for calves transported by road and ferry from Ireland to the Netherlands and to investigate the effect of journey [two comparable journeys in April (J1) and May (J2) 2022] and source [source farm or mart (SF/MA)] on these variables. A total of 66 calves from the SF/MA were transported from Ireland to commercial veal farms in the Netherlands. Blood samples were collected at the SF/MA, assembly center (Ireland), lairage (France), and on arrival on the veal farm (Netherlands). They were analyzed for indicator variables related to energy balance, hydration/electrolytes, physical/muscular stress, immunity, and inflammation [glucose, beta-hydroxybutyrate (BHB), non-esterified fatty acids (NEFA), potassium, sodium, magnesium, chloride, urea, haematocrit, total protein, creatine kinase, L-lactate, cortisol, white blood cell, neutrophil, lymphocyte and monocyte counts, serum amyloid-A, and haptoglobin]. Health variables eye and nose discharge, skin tent (a measure of dehydration), and navel inflammation were scored by a trained observer, and calves were weighed at every blood-sampling time point. All blood variables and body weight changed significantly ( < 0.05) during transport, most notably between the assembly center and lairage. Reference ranges were available for 18 variables; 11 of these variables exceeded the reference ranges at the lairage, whilst 10 variables exceeded the reference ranges on arrival at the veal farm. However, health variables did not change during transport. A journey-to-journey comparison indicated much variation; 18 out of 25 variables differed significantly on at least one time point. In total, J1 calves experienced a more severe change in BHB, potassium, strong-ion-difference, L-lactate, and eye and nose discharge than J2 calves. The source of calves also affected their physiology; 12 out of 25 variables studied differed significantly, all of which were confined to the first time point. Specifically, MA calves had elevated levels of NEFA, urea, haematocrit, L-lactate, cortisol, white blood cell, neutrophil, and monocyte counts and lower levels of corrected chloride and lymphocyte count. Overall, calves in this study showed a generalized physiological disturbance beyond reference limits during long-distance transport, but no animal died during transport or for 3 weeks post-arrival.
PubMed: 37829357
DOI: 10.3389/fvets.2023.1238734