scholarly journals Circulating Ionized Magnesium as a Measure of Supplement Bioavailability: Results from a Pilot Study for Randomized Clinical Trial

Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1245 ◽  
Author(s):  
Jiada Zhan ◽  
Taylor C. Wallace ◽  
Sarah J. Butts ◽  
Sisi Cao ◽  
Velarie Ansu ◽  
...  

Oral supplementation may improve the dietary intake of magnesium, which has been identified as a shortfall nutrient. We conducted a pilot study to evaluate appropriate methods for assessing responses to the ingestion of oral magnesium supplements, including ionized magnesium in whole blood (iMg2+) concentration, serum total magnesium concentration, and total urinary magnesium content. In a single-blinded crossover study, 17 healthy adults were randomly assigned to consume 300 mg of magnesium from MgCl2 (ReMag®, a picosized magnesium formulation) or placebo, while having a low-magnesium breakfast. Blood and urine samples were obtained for the measurement of iMg2+, serum total magnesium, and total urine magnesium, during 24 h following the magnesium supplement or placebo dosing. Bioavailability was assessed using area-under-the-curve (AUC) as well as maximum (Cmax) and time-to-maximum (Tmax) concentration. Depending on normality, data were expressed as the mean ± standard deviation or median (range), and differences between responses to MgCl2 or placebo were measured using the paired t-test or Wilcoxon signed-rank test. Following MgCl2 administration versus placebo administration, we observed significantly greater increases in iMg2+ concentrations (AUC = 1.51 ± 0.96 vs. 0.84 ± 0.82 mg/dL•24h; Cmax = 1.38 ± 0.13 vs. 1.32 ± 0.07 mg/dL, respectively; both p < 0.05) but not in serum total magnesium (AUC = 27.00 [0, 172.93] vs. 14.55 [0, 91.18] mg/dL•24h; Cmax = 2.38 [1.97, 4.01] vs. 2.24 [1.98, 4.31] mg/dL) or in urinary magnesium (AUC = 201.74 ± 161.63 vs. 139.30 ± 92.84 mg•24h; Cmax = 26.12 [12.91, 88.63] vs. 24.38 [13.51, 81.51] mg/dL; p > 0.05). Whole blood iMg2+ may be a more sensitive measure of acute oral intake of magnesium compared to serum and urinary magnesium and may be preferred for assessing supplement bioavailability.

BMC Urology ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Clemens Wiesinger ◽  
Dominik Stefan Schoeb ◽  
Mathias Stockhammer ◽  
Emir Mirtezani ◽  
Lukas Mitterschiffthaler ◽  
...  

Abstract Background Within the last decade, robotically-assisted laparoscopic prostatectomy (RALP) has become the standard for treating localized prostate cancer, causing a revival of the 45° Trendelenburg position. In this pilot study we investigated effects of Trendelenburg position on hemodynamics and cerebral oxygenation in patients undergoing RALP. Methods We enrolled 58 patients undergoing RALP and 22 patients undergoing robot-assisted partial nephrectomy (RAPN) (control group) in our study. Demographic patient data and intraoperative parameters including cerebral oxygenation and cerebral hemodynamics were recorded for all patients. Cerebral function was also assessed pre- and postoperatively via the Mini Mental Status (MMS) exam. Changes in parameters during surgery were modelled by a mixed effects model; changes in the MMS result were evaluated using the Wilcoxon signed rank test. Results Preoperative assessment of patient characteristics, standard blood values and vital parameters revealed no difference between the two groups. Conclusions Applying a 45° Trendelenburg position causes no difference in postoperative brain function, and does not alter cerebral oxygenation during a surgical procedure lasting up to 5 h. Further studies in larger patient cohorts will have to confirm these findings. Trial registration German Clinical Trial Registry; DRKS00005094; Registered 12th December 2013—Retrospectively registered; https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00005094.


2019 ◽  
Vol 47 (2) ◽  
pp. 190-194 ◽  
Author(s):  
Bernhard Stoiber ◽  
Christian Haslinger ◽  
Marie Kristin Schäffer ◽  
Roland Zimmermann ◽  
Leonhard Schäffer

Abstract Objectives To measure the tocolytic effect of the combination of the oxytocin receptor antagonist atosiban with the β-mimetic agent fenoterol on human myometrium of pregnant women. Methods An in vitro study of contractility in human myometrium at the Laboratory of the Department of Obstetrics, University Hospital of Zürich, Switzerland, was performed. Thirty-six human myometrial biopsies were obtained during elective caesarean sections of singleton pregnancies at term. Tissue samples were exposed to atosiban, fenoterol and the combination of atosiban with fenoterol. Contractility was measured as area under the curve during 30 min of spontaneous contractions. The effect of treatment was expressed as the percentage of change from basal activity during 30 min of exposure. Differences were calculated using a paired Wilcoxon signed-rank test. An additive effect of dual tocolysis was assumed when no significant difference was detected between the observed and expected inhibition of dual tocolysis. When inhibition was greater or lower than expected, the dual combination was characterised as “synergistic” or “antagonistic”, respectively. Results Atosiban and fenoterol alone suppressed contractions by a median of 43.2% and 29.8%, respectively. The combination of atosiban plus fenoterol was measured at a level of 67.3% inhibition. There was no significant difference in the expected (63.2%) and observed inhibition effect of dual tocolysis (P=0.945). Conclusion This study demonstrated an additive effect of dual tocolysis of atosiban and fenoterol on human myometrium in vitro, but no synergistic or antagonistic effect.


2020 ◽  
Author(s):  
Steve Durante ◽  
Vincent Dunet ◽  
François Gorostidi ◽  
Periklis Mitsakis ◽  
Niklaus Schaefer ◽  
...  

Abstract Background : Angiogenesis plays an important role in head and neck squamous cell carcinomas (HNSCC) progression. This pilot study was designed to compare the distribution of 68 Ga-NODAGA-RGD PET/CT for imaging α v β 3 integrins involved in tumor angiogenesis to 18 F-FDG PET/CT in patients with HNSCC. Material and methods : Ten patients (aged: 58.4 ± 8.3 years [range: 44–73 years], 6 males, 4 females) with a total of 11 HNSCC were prospectively enrolled. Activity mapping and standard uptake values (SUV) from both 68 Ga -NODAGA-RGD and 18 F-FDG PET/CT scans were recorded for primary tumor and compared with the Wilcoxon signed-rank test. The relation between the SUV of both tracers was assessed using the Spearman correlation. Results : All HNSCC tumors were visible with both tracers. Quantitative analysis showed higher 18 F-FDG SUV max in comparison to 68 Ga-NODAGA-RGD (14.0 ± 6.1 versus 3.9 ± 1.1 g/mL, p=0.0017) and SUV mean (8.2 ± 3.1 versus 2.0 ± 0.8 g/mL, p=0.0017). Both 18 F-FDG and 68 Ga-NODAGA-RGD uptake were neither correlated with grade, HPV nor p16 protein expression (p≥0.17). Conclusion : All HNSCC tumors were detected with both tracers with higher uptake with 18 F-FDG, however. 68 Ga-NODAGA-RGD has a different spatial distribution than 18 F-FDG bringing different tumor information.


2002 ◽  
Vol 126 (8) ◽  
pp. 947-950 ◽  
Author(s):  
Sihe Wang ◽  
Elizabeth H. McDonnell ◽  
Frank A. Sedor ◽  
John G. Toffaletti

Abstract Context.—It is well known that the concentration of ionized calcium in blood is affected by the pH of the specimen, since hydrogen ions compete with calcium for binding sites on albumin and other proteins. However, the relationship between pH and ionized magnesium concentration is not as well characterized. Objective.—To determine the effects of pH on ionized magnesium concentration over a wide range of pH values in serum or plasma. Design.—Both ionized calcium and ionized magnesium concentrations were measured in 3 sets of samples. (1) Pools of serum or whole blood at different pH values (7.20–7.60) achieved by adding a constant volume of acid or base (diluted solutions of either hydrochloric acid or sodium hydroxide) plus saline. These pools consisted of 2 serum and 3 heparinized whole blood pools collected from leftover blood remaining in clinical specimens in the Clinical Chemistry and Blood Gas Laboratories, respectively, at Duke University Medical Center. (2) Five whole blood specimens obtained from apparently healthy individual donors. (3) Twenty-six whole blood specimens obtained from individual patients (leftover blood from the Blood Gas Laboratory) in which pH was varied by in vitro loss or gain of carbon dioxide. Results.—Both ionized calcium and ionized magnesium concentrations decreased as the pH in the specimen increased, indicating the stronger binding of these ions with proteins in the more alkaline environment. Conclusion.—We conclude that the rate of change of ionized magnesium concentration with pH change (0.12 mmol/L per pH unit) is significantly less than that of ionized calcium (0.36 mmol/L per pH unit). Furthermore, our findings indicate that if adjustment to pH 7.40 is necessary, the ionized magnesium test results need to be adjusted when pH is markedly abnormal, as is sometimes done for ionized calcium.


Cephalalgia ◽  
1993 ◽  
Vol 13 (6) ◽  
pp. 410-412 ◽  
Author(s):  
R Hering ◽  
V Glover ◽  
K Pattichis ◽  
T Catarci ◽  
TJ Steiner

Whole blood 5HT levels were measured in seven female migraine sufferers with chronic daily headache due to medication abuse, before and after abrupt medication withdrawal. A statistically significant increase in 5HT levels, from mean 4.89 mmol/1 to mean 6.59 mmol/I ( p < 0.05, Wilcoxon signed rank test), as well as a significant improvement in the number of headache-free days ( p < 0.05, Wilcoxon signed rank test), occurred after 4 weeks of withdrawal. We conclude from this pilot study that 5HT may be important in the physiopathogenesis of chronic daily headache. Alternatively, reduced 5HT may be the result of chronic daily headache or else an epiphenomenon.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 3032-3032 ◽  
Author(s):  
C. F. Mojcik ◽  
N. S. Young ◽  
L. Luzzatto ◽  
G. Socié ◽  
P. Hillmen ◽  
...  

3032 Background: Erythropoietins (EPO) are commonly used to improve anemia in patients with bone marrow failure syndromes and in patients with chemotherapy-induced anemia. Two recent phase 3 clinical studies have demonstrated significant benefit of the terminal complement inhibitor, eculizumab (Soliris), in a heterogeneous population of patients with the acquired clonal hemolytic and bone marrow failure disorder, PNH (n=140). While previous studies have shown that EPO is associated with only moderate improvements in fatigue in anemic cancer patients (effect size of 0.5), eculizumab has demonstrated large improvements in fatigue in PNH patients (effect size of 1.1). Methods: To investigate whether eculizumab provides further benefit to PNH patients receiving EPO, efficacy parameters were examined in the EPO subpopulation (n=8). Results: Intravascular hemolysis, as assessed by plasma levels of lactate dehydrogenase (LDH) area under the curve, was reduced 268,271 U/L x day to near normal levels in EPO-treated patients during 26 weeks of eculizumab therapy (p=0.008, signed rank test). Anemia was improved as packed RBC transfusion requirements were substantially reduced with eculizumab in EPO patients from a median of 7.5 units per patient in the 6 months before treatment to 1 unit per patient during eculizumab treatment (p=0.031, signed rank test). Despite pre-existing EPO and transfusion support, eculizumab treatment markedly improved fatigue with a 7.3 point increase over baseline using the FACIT-fatigue instrument (p=0.016, signed rank test; a 3 or more point increase in this instrument has been shown to be clinically meaningful). Eculizumab was well tolerated when administered to PNH patients treated with concomitant EPO with adverse events similar to the overall population. The significant clinical improvements in hematologic and quality of life outcomes with eculizumab treatment in PNH patients receiving concomitant EPO were similar to the clinical improvements demonstrated in the overall PNH patient population. Conclusions: These analyses show that eculizumab treatment provides important clinical benefit when administered to PNH patients receiving EPO support for bone marrow failure. No significant financial relationships to disclose.


Blood ◽  
1996 ◽  
Vol 87 (9) ◽  
pp. 3650-3654 ◽  
Author(s):  
E Estey ◽  
PF Thall ◽  
K Mehta ◽  
M Rosenblum ◽  
T Jr Brewer ◽  
...  

We administered liposome-encapsulated all-trans retinoic acid (L-ATRA) to 48 patients with refractory hematologic malignancies using an every- other-day schedule for 28 days and doses of 15 to 175 mg/m2. In 19 patients, pharmacology studies were conducted after the first (day 1) and seventh (day 15) doses. In contrast to the decline in tretinoin concentration seen within 3 to 4 days of administration of daily oral ATRA, there were no differences between the area under the curve (AUC) of tretinoin concentration versus time on day 1 and day 15 (P = .98, Wilcoxon signed-rank test). Peak day 1 concentrations after 15 mg/m2 were higher than those reported after 45 mg/m2 oral ATRA. Six patients with relapsed acute promyelocytic leukemia (APL) were treated. Three, each in first relapse and at least year from the last exposure to oral ATRA, achieved a complete response (CR). Disease recurred in two (one at 3 months despite maintenance L-ATRA and similarity in tretinoin AUC on days 1 and 85, and the other at 5 months, 2 months after discontinuation of L-ATRA) and the third was transplanted 1 month into CR. The three nonresponders were in at least a second relapse and failed to respond to oral ATRA before or immediately after receiving L- ATRA. Severe toxicity developed in three of eight patients treated at 175 mg/m2 (joint pains in two, skin in one). The maximum tolerated dose (MTD) was determined to be 140 mg/m2, at which dose grade 2 toxicity (primarily headache and skin) occurred in eight of eight patients, but grade 3 to 4 toxicity in none. Compared with oral ATRA, L-ATRA apparently results in greater exposure to tretinoin and for a longer time.


Author(s):  
Rebecca L. Heron ◽  
Lena Schwiekert ◽  
Julie Karsten

AbstractPeople with pedophilia (PWP) are highly stigmatized. Public opinion is strongly pre-consolidated – it is often assumed that every PWP commits child sex offenses. This presumption not only affects PWP negatively. Research suggests that this stigmatization may cohere with PWP actually committing child sex offenses. Various recent studies have investigated different kinds of anti-stigma interventions and their effectiveness. Direct contact to a PWP has not yet been investigated. The present pilot study aimed at finding out whether a dichotomous anti-stigma intervention can change psychology students’ attitudes towards PWP regarding perceived dangerousness, intentionality, deviance, and punitive attitudes. In a one sample pre-post design, we presented 162 students of the University of Groningen with both an educational lecture and direct contact to a PWP. Participants learned about child sex offending and pedophilia. Then, Gabriel, a PWP shared his experiences about growing up, coping, and living with pedophilia. Results of the one-sample Wilcoxon signed-rank test revealed significantly diminished negative attitudes towards PWP after the intervention. Students perceived PWP as less dangerous, having less intent, and being less psychologically deviant. Additionally, students’ punitive attitudes towards PWP diminished significantly. Also, a thematic analysis revealed that students were highly interested in the topic of pedophilia and greatly appreciative of Gabriel sharing his story. This pilot study was the first to provide evidence for the effectiveness of a combination of an educational lecture and direct contact to a PWP as an anti-stigma intervention.


1976 ◽  
Vol 68 (2) ◽  
pp. 159-178 ◽  
Author(s):  
P De Weer

The free magnesium concentration in the axoplasm of the giant axon of the squid, Loligo pealei, was estimated by exploting the known sensitivity of the sodium pump to intracellular Mg2+ levels. The Mg-citrate buffer which, when injected into the axon, resulted in no change in sodium efflux was in equilibrium with a Mg2+ level of about 3--4 mM. Optimal [Mg2+] for the sodium pump is somewhat higher. Total magnesium content of axoplasm was 6.7 mmol/kg, and that of hemolymph was 44 mM. The rate coefficient for 28Mg efflux was about 2 X 10(-3) min-u for a 500-mum axon at 22-25degreesC, with a very high temperature coefficient (Q10=4-5). This efflux is inhibited 95% by injection of apyrase and 75% by removal of external sodium, and seems unaffected by membrane potential or potassium ions. Increased intracellular ADP levels do not affect Mg efflux nor its requirement for Na+/o, but extracellularl magnesium ions do. Activation of 28Mg efflux by Na+/o follows hyperbolic kinetics, with Mg2+/o reducing the affinity of the system for Na+/o. Lanthanum and D600 reversibly inhibit Mg efflux. In the absence of both Na+ and Mg2+, but not in their presence, removal of Ca2+ from the seawater vastly increased 28Mg efflux; this efflux was also strongly inhibited by lanthanum. A small (10(-14) mol cm-2) extra Mg efflux accompanies the conduction of an action potential.


2019 ◽  
Vol 29 (3) ◽  
pp. 7-11
Author(s):  
Simone A. Majetich ◽  
Michael W. Majetich ◽  
James M. Clegg ◽  
Susan M. Ratay

Abstract Context The use of osteopathic manipulative medicine (OMM) continues to decline in medical practice, despite an increasing number of osteopathic physicians. Objective This pilot study was designed to determine if a brochure created to increase knowledge about osteopathic medicine and OMM was read by patients, reviewed as being helpful, needed modifications and increased patient understanding of and willingness to receive OMM in preparation for a large scale trial that will assess this in both the hospital and ambulatory settings. Methods The study was performed using an educational brochure and 2 closed questionnaires. Twenty-seven patients of either inpatient or observation status aged 18 and above with English literacy were enrolled. Participants first completed a pre-questionnaire with questions regarding understanding of OMM and willingness to receive treatment. They then read the provided educational brochure, which contained a checkbox to verify the material was read in its entirety. Participants completed a post-questionnaire with similar questions. The results were analyzed with Wilcoxon signed rank test with 95% confidence to observe any changes in pre- and post-questionnaire responses. Results Of the participants, 48.1% provided verification that they read the brochure. A significant increase in patient willingness to receive OMM as part of their treatment regimen was observed for those who read the brochure (P=.008 ). No significant change was seen for those who didn’t read the brochure (P=.26). Additionally, 100% of participants indicated that the brochure was helpful, and 100% of participants indicated a better understanding of OMM. Cost remained a significant barrier to accepting or pursuing OMM treatment. Conclusion This pilot study demonstrated a statistically significant improvement in willingness to receive treatment after reviewing the designed brochure. It also identified a need to convey information regarding cost of OMM treatment to patients and a need to better emphasize the checkbox located within the brochure for verification purposes. The brochure and study design proved feasible and will provide the foundation for a larger scale trial looking to assess if a patient educational handout improves understanding of OMM and willingness to receive treatment in the hospital and ambulatory settings.


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